Fisioterapia durante o transplante de células tronco hematopoiéticas alogênico para o tratamento de anemia aplásica: um relato de caso considerado raro / Physical therapy during allogeneic hematopoietic stem cell transplantation for the treatment of aplastic anemia: a rare clinical case

Introdução: A anemia aplásica (AA) é uma condição clínica considerada rara que se desenvolve a partir da disfunção hematopoiética da medula óssea. O tratamento indicado é o transplante de células tronco hematopoiéticas (TCHP). Objetivo: Descrever o caso clínico e as estratégias utilizadas pela fisioterapia durante o processo de reabilitação física. Métodos: Trata-se de estudo de caso, realizado com paciente do sexo feminino, 34 anos de idade e diagnóstico de AA severa. Após avaliação clínica foi indicado o TCHP alogênico de um doador aparentado que apresentou compatibilidade histo-imunológica. O tempo total de internação hospitalar foi de 35 dias. Os objetivos da reabilitação física foram o de manter a ventilação pulmonar, prevenir o acúmulo de secreção, minimizar a progressão da fadiga, perda de força e resistência muscular. Resultados: A estratégia utilizada para contornar a extrema fragilidade hematológica e as implicações clínicas decorrentes evitou perda expressiva no desempenho no teste de caminhada de seis minutos (-10%) ao final da internação. Conclusão: Foi um verdadeiro desafio a implementação da reabilitação física durante o TCHP para o tratamento da AA, mas a estratégia adotada demonstrou-se segura, bem tolerada e suficiente para evitar maiores prejuízos no estado funcional. (AU)

Research progress of Notch signaling pathway in spinal cord injury / 中国骨伤

Spinal cord injury is a severe central nervous system disease, which will cause a series of complex pathophysiological changes and activate a variety of signaling pathways including Notch signaling. Studies have evidenced that activation of the Notch signaling pathway is not conducive to nerve repair and symptom improvement after spinal cord injury. Its mechanisms include inhibiting neuronal differentiation and axon regeneration, promoting reactive astrocyte proliferation, promoting M1 macrophage polarization and the release of proinflammatory factors, and inhibiting angiogenesis. Therefore, it has become a promising therapeutic strategy to inhibit Notch signal as a target in the treatment of spinal cord injury. In recent years, some researchers have used drugs, cell transplantation or genetic modification to regulate Notch signaling, which can promote the recovery of nerve function after spinal cord injury, thereby providing new treatment strategies for the treatment of spinal cord injury. This article will summarize the mechanism of Notch signaling pathway in spinal cord injury, and at the same time review the research progress in the treatment of spinal cord injury by modulating Notch signaling pathway in recent years, so as to provide new research ideas for further exploring new strategies for spinal cord injury.

Advances in olfactory ensheathing cells for the treatment of spinal cord injury / 中国骨伤

Spinal cord injury is a highly disabled neurological disease, and there is still a lack of effective treatments. Studies have proved that olfactory ensheathing cells are one of the ideal seed cells for promoting nerve regeneration after spinal cord injury. Olfactory ensheathing cells can promote axonal germination and elongation through secretion, interaction with astrocytes, regulation of inflammatory reaction, migration characteristics, myelination, anti-oxidation, lipid regulation and other channels. Thus olfactory ensheathing cells play the role of neuroprotection and nerve repair. In recent years, some studies have used bioengineering, tissue engineering, reprogramming and other technologies to enhance the efficacy of olfactoryensheathing cells from different aspects, thereby providing new therapeutic strategies for optimizing the cell therapy of spinal cord injury. This article will summarize the mechanism of olfactory ensheathing cells in repairing spinal cord injury, and review the progress of optimizing strategy of olfactory ensheathing cells in treating spinal cord injury recently, so as to provide new research ideas for the further developing the repair potential of olfactory ensheathing cells and optimize the cell therapy effect of spinal cord injury.

A double fluorescence chimeric limb regeneration model reveals muscle fiber reconnection during axolotl limb regeneration / Modelo de regeneración quimérica de doble fluorescencia del miembro revela la reconexión de la fibra muscular durante la regeneración del miembro axolotl

SUMMARY: Axolotl limb regeneration is a fascinating characteristic that has attracted attention for several decades. Our previous studies on axolotl limb regeneration indicated that the satellite cells in the remnant muscles move distally into the blastema to regenerate new muscles that are separated by a gap from remnant muscles. Thereafter, the regenerative muscle fibers start to reconnect with remnant ones. In this study, the reconnection at the individual muscle fiber level was elucidated to test the hypothesis that this reconnection happens synchronously among involved muscles. Three pairs of EGFP+ mid-bud stage blastemas were transplanted onto freshly amputated stumps of RFP+ axolotls at the same thigh position to generate double fluorescence chimeric regenerative hindlimbs. These regenerative limbs were harvested very late far beyond they had reached the late differentiation stage. Fluorescence imaging of these limbs in cross sections revealed that in the proximal remnant part of the muscle fiber, reconnection occurred at a different pace among the muscles. In the major thigh muscle gracilis, the reconnection started from the periphery before it was completed. Furthermore, RFP+ muscle fibers contributed to muscle regeneration in the distal regenerative parts. Intriguingly, this red cell contribution was limited to ventral superficial muscles of the calf. This kind of double fluorescence chimeric limb regeneration model may help increase the understanding of the patterning of axolotl limb regeneration in late stages.

RESUMEN: La regeneración del miembro de Axolotl es una característica fascinante que ha llamado la atención durante varias décadas. Nuestros estudios previos sobre la regeneración del miembro del Axolotl indicaron que las células satélite en los músculos remanentes se mueven distalmente hacia el blastema para regenerar nuevos músculos que están separados por una brecha de músculos remanentes. A partir de entonces, las fibras musculares regenerativas comienzan a reconectarse con las restantes. En este estudio, se aclaró la reconexión a nivel de fibra muscular individual para probar la hipótesis de que esta reconexión ocurre sincrónicamente entre los músculos involucrados. Se trasplantaron tres pares de blastemas EGFP+ en la etapa de yema media en tocones recién amputados de axolotls RFP+ en la misma posición del muslo para generar miembros posteriores regenerativos quiméricos de fluorescencia doble. Estos miembros regenerativos se cosecharon muy tarde mucho más allá de haber alcanzado la etapa de diferenciación tardía. Las imágenes de fluorescencia de estos miembros en secciones transversales revelaron que en la parte remanente proximal de la fibra muscular, la reconexión se produjo a un ritmo diferente entre los músculos. En el músculo grácil, la reconexión comenzó desde la periferia antes de completarse. Además, las fibras musculares RFP+ contribuyeron a la regeneración muscular en las partes regenerativas distales. Curiosamente, esta contribución de glóbulos rojos se limitó a los músculos superficiales ventrales de la pantorrilla. Este tipo de modelo de regeneración quimérica de doble fluorescencia del miembro puede ayudar a aumentar la comprensión del patrón de la regeneración del miembro del Axolotl en etapas tardías.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.

Outcome and prognostic factors of children with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib followed by allogeneic hematopoietic cell transplantation in first remission

BACKGROUND: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a subset of ALL with poor prognosis. Here, we analyzed the outcomes and prognostic factors of children with Ph+ ALL who received imatinib and chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR). METHODS: Thirty-one Ph+ ALL patients (female 10) diagnosed from January 2005 to December 2016 were included in the study. All patients were treated with imatinib and chemotherapy before HCT. Bone marrow (BM) evaluations included real-time quantitative polymerase chain reaction (RQ-PCR) study of the BCR-ABL1 fusion transcript. All patients received HCT with total body irradiation (TBI)-based conditioning at a median of 6.4 (range, 4.2–47.1) months from diagnosis. RESULTS: Compared to values at diagnosis, the median decrement of RQ-PCR value post-consolidation, and prior to HCT was −3.7 Log and −4.8 Log, respectively. The 5-year event-free survival (EFS) and overall survival of the patients were 64.5±9.4% (20/31) and 75.0±8.3% (23/31) respectively. Events included relapse (N=5) and death in CR post-HCT (N=6). The 5-year incidence of molecular relapse was 30.9±9.1% (9/31). An RQ-PCR decrement of at least −4 Log post-consolidation significantly predicted lower incidence of molecular relapse: 7.7±7.7% for ≥−4 Log decrement, 50.0±13.8% for <−4 Log decrement (P=0.027). CONCLUSION: Decrement in RQ-PCR for the BCR-ABL1 transcript that was determined after consolidation was the only significant prognostic factor for incidence of molecular relapse. In the post-induction TKI initiation setting, steadfast imatinib treatment during consolidation may allow for optimum post-HCT outcomes.

Apoptosis, nutrition, and metabolism of transplanted intervertebral disc cells / Apoptose, nutrição e metabolismo de células de discos intervertebrais transplantadas / Apoptosis, nutrición y metabolismo de las células de discos intervertebrales trasplantadas

ABSTRACT Introduction: Apoptosis is a contributing factor to degenerating intervertebral disc (IVD). Disc regeneration has been attempted by transplanting cells into the disc, with some gains in disc height achieved in animal models. Here, we study whether the apoptotic microenvironment affects the transplanted disc cells. Methods: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were grown in media then starved for 5 days in vitro by not changing the media. Three aspects of apoptotic cell influence on the transplanted cells were tested in a total of 32 samples: 1) the effect of apoptotic cytokines in the media, 2) reduced glucose in the media, and 3) apoptotic cell bodies in the flask. The Trypan Blue, AlamarBlue®, and 1,9-Dimethyl-Methylene Blue assays for sulfated glycosaminoglycan (sGAG) content were performed (n=4). Results: There were significant decreases in cell viability between the control, 25% conditioned media (CM) and starved control group. There were no significant differences in cell number, metabolic activity or sGAG production in cells grown in different conditioned media compared to cells grown in complete media. The cells of the control decreased in viability and number over the 5 days without feeding, then improved dramatically when feeding was resumed. Flasks that received transplanted cells in addition to renewed feeding did not recover as much as the cells in the re-fed group. Conclusions: Cytokines from starved cells negatively impact on the viability of healthy cells. Starving cells that receive new sources of nutrition have even higher viability than transplanted cells. This indicates that altering and improving the nutrient supply problem in the IVD could be a valuable option. Level of Evidence III; Case control studyg.

RESUMO Introdução: A apoptose é um fator que contribui para a degeneração do disco intervertebral (DIV). A tentativa de regenerar o disco foi por meio de transplante de células no disco, com alguns ganhos de altura do disco alcançados em modelos animais. Aqui estudamos se o microambiente apoptótico afeta as células do disco transplantadas. Métodos: Células humanas do ânulo fibroso (AF) e do núcleo pulposo (NP) foram cultivadas in vitro em meio de cultura e privadas de nutrição por cinco dias, sem alteração dos meios. Três aspectos da influência de células apoptóticas em células transplantadas foram testados em um total de 32 amostras: 1) o efeito de citocinas apoptóticas no meio de cultura, 2) redução de glicose no meio e 3) corpos celulares apoptóticos no frasco. Realizaram-se ensaios com azul de tripano, AlamarBlue® e 1,9-dimetil azul de metileno para o teor de glicosaminoglicano sulfatado (sGAG) (n = 4). Resultados: Constataram-se decréscimos significativos na viabilidade celular entre o grupo controle, meio condicionado (MC) a 25% e grupo controle privado de nutrição. Não houve diferenças significativas no número de células, atividade metabólica ou produção de sGAG em células cultivadas em diferentes meios condicionados em comparação com o meio completo. As células de controle tiveram redução de viabilidade e de número ao longo dos 5 dias sem alimentação; a seguir, houve melhorara substancial ao se retomar a alimentação. Os frascos que receberam células transplantadas, além da alimentação renovada, não se recuperaram tanto quanto as células do grupo realimentado. Conclusões: As citocinas de células famintas tiveram impacto negativo sobre a viabilidade das células saudáveis. As células famintas que recebem novas fontes de nutrição têm viabilidade ainda maior do que as células transplantadas. Isso indica que alterar e melhorar o fornecimento de nutrientes no DIV pode ser uma opção valiosa. Nível de Evidência III; Estudo de caso controleg.

RESUMEN Introducción: La apoptosis es un factor que contribuye a la degeneración del disco intervertebral (DIV). El intento de regenerar el disco fue por medio de trasplante de células en el disco, con el que se ganó el aumento de altura del disco logrado en modelos animales. Aquí estudiamos si el microambiente apoptótico afecta a las células del disco trasplantadas. Métodos: Células humanas del anillo fibroso (AF) humano y del núcleo pulposo (NP) fueron cultivadas in vitro en medio de cultivo y privadas de nutrición por 5 días, sin alteración de los medios. Tres aspectos de la influencia de las células apoptóticas trasplantadas se probaron en un total de 32 muestras: 1) el efecto de las citoquinas apoptóticas en el medio de cultivo, 2) reducción de la glucosa en el medio y 3) los cuerpos celulares apoptóticos en el matraz. Se realizaron ensayos con azul de tripano, AlamarBlue® y 1,9-dimetil-azul de metileno para el contenido de glicosaminoglicano sulfatado (sGAG) (n = 4). Resultados: Se constataron disminuciones significativas de la viabilidad celular entre el grupo control, medio condicionado (MC) al 25% y el grupo control privado de nutrición. No hubo diferencias significativas en el número de células, la actividad metabólica o producción de sGAG en células cultivadas en diferentes medios condicionados en comparación con el medio completo. Las células de control tuvieron reducción de viabilidad y de número a lo largo de los 5 días sin alimentación; luego, hubo una mejora sustancial al reanudar la alimentación. Los matraces que recibieron células trasplantadas, además de la alimentación renovada, no se recuperaron tanto como las células del grupo alimentado nuevamente. Conclusiones: Las citoquinas de las células privadas de alimento tuvieron un impacto negativo en la viabilidad de las células sanas. Las células hambrientas que reciben nuevas fuentes de nutrición tienen mayor viabilidad que las células trasplantadas. Esto indica que cambiar y mejorar suministro de nutrientes en el DIV puede ser una opción valiosa. Nivel de Evidencia III; Estudio de caso controlg.

Implante de células madre en fractura de cadera. Presentación de un Caso / Stem cells implant in hip fracture. Case presentation

Introducción: Las fracturas de cadera son muy frecuentes en el anciano, la primera fase de consolidación de una fractura es el hematoma creado a este nivel, si éste se enriquece con células madre adultas autólogas podría disminuir el tiempo de consolidación de la fractura debido a la gran capacidad que tienen estas células para transformarse en otros tipos de tejido. Objetivo: Evidenciar las ventajas del implante de las células madre en un paciente con fractura reciente de cadera. Presentación del caso: paciente con fractura de cadera que se operó en las primeras 24 horas y que durante su intervención se le implantaron células monoculares (células madre) obtenidas de su pelvis. Conclusiones: Se demostró la factibilidad de dicho proceder y la buena evolución del paciente, sin complicaciones y una consolidación precoz(AU)

Introduction: Hip fractures are very common in the elderly. It is known that the first phase of fracture healing is a local hematoma, and if it is enriched with autologous stem cells, hip fracture healing time could be diminished due to the great capacity these cells have to turn into other types of tissues. Objective: To show the advantages of the stem cells implant in a patient with a hip fracture Case presentation: A patient with a hip fracture underwent surgery during the first 24 hours after fracture and during the surgical procedure, monocular stem cells obtained from his pelvis were implanted. Conclusions: The feasibility of the stem cells implant in a hip fracture without complications and earlier healing was demonstrated(AU)

Research advances in immune tolerance of allogeneic cell transplantation in preterm infants / 中国当代儿科杂志

Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.

Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome

BACKGROUND: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. METHODS: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. RESULTS: The median time from HCT to relapse was 6.6 (range, 0.9–136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. CONCLUSION: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Mesenchymal Stromal Cells from the Maternal Segment of Human Umbilical Cord is Ideal for Bone Regeneration in Allogenic Setting

Umbilical cord (UC) is a discarded product from the operating theatre and a ready source of mesenchymal stromal cells (MSCs). MSCs from UC express both embryonic and adult mesenchymal stem cell markers and are known to be hypoimmunogenic and non-tumorigenic and thus suitable for allogeneic cell transplantation. Our study aimed to determine the degree of immunotolerance and bone-forming capacity of osteodifferentiated human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) from different segments of UC in an allogenic setting. UCs were obtained from healthy donors delivering a full-term infant by elective Caesarean section. hWJ-MSCs were isolated from 3 cm length segment from the maternal and foetal ends of UCs. Three-dimensional fibrin constructs were formed and implanted intramuscularly into immunocompetent mice. The mice were implanted with 1) fibrin construct with maternal hWJ-MSCs, 2) fibrin construct with foetal hWJ-MSCs, or 3) fibrin without cells; the control group received sham surgery. After 1 month, the lymphoid organs were analysed to determine the degree of immune rejection and bone constructs were analysed to determine the amount of bone formed. A pronounced immune reaction was noted in the fibrin group. The maternal segment constructs demonstrated greater osteogenesis than the foetal segment constructs. Both maternal and foetal segment constructs caused minimal immune reaction and thus appear to be safe for allogeneic bone transplant. The suppression of inflammation may be a result of increased anti-inflammatory cytokine production mediated by the hWJ-MSC. In summary, this study demonstrates the feasibility of using bone constructs derived from hWJ-MSCs in an allogenic setting.

Estudio bibliométrico: 45 años de literatura biomédica en trasplante de células madre hematopoyéticas / A Bibliometric Study: 45 Years of Biomedical Literature in Hematopoietic Stem Cell Transplantation / Estudo bibliométrico: 45 anos de literatura biomédica em transplante de células-tronco hematopoiéticas

Introducción: La bibliometría mide variables de la literatura científica que se describen de forma cuantitativa por medio de análisis estadístico; con esta herramienta se busca evidenciar el impacto de los trasplantes de células madre hematopoyéticas en la literatura de los últimos 45 años. Objetivo: Descripción de la literatura médica indexada en MEDLINE desde 1970 hasta 2015 sobre trasplantes de células madre hematopoyéticas. Metodología: Se realizó una búsqueda en la base de datos MEDLINE a través de GoPubMed y Fabumed. La estrategia de búsqueda fue: "Hematopoietic Stem Cell Transplantation" [Majr] AND "1970:2015"[dp]. Las variables analizadas fueron el número de publicaciones por año, revistas, países y porcentaje de publicaciones sobre trasplantes de células madre hematopoyéticas. Resultados: Se recuperaron 23,295 referencias sobre trasplantes de células madre hematopoyéticas. Se identificaron 1,844 revistas diferentes, el mayor número de publicaciones se encontró en Bone Marrow Transplantation con 2,443 publicaciones, seguida de Blood con 1,375 y Biology of Bone Marrow Transplantation con 1,319 referencias. Estados Unidos fue el país con mayor número de publicaciones con 7,491 (32.15%); en Latinoamérica fueron publicados 324 (1.39%). Los descriptores de la literatura más investigados relacionados con el tema fueron: Trasplante de células madre hematopoyéticas con 23,345 publicaciones, humanos con 22,019 y células madre con 17,564. Conclusiones: Las publicaciones sobre trasplantes de células madre hematopoyéticas han incrementado de forma progresiva durante los 45 años estudiados. Los países desarrollados son los que han realizado mayor investigación del tema, en contraste con el número de publicaciones en total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. Estudio bibliométrico: 45 años de literatura biomédica en trasplante de células madre hematopoyéticas. MedUNAB 2017-2018; 20(3): 319-326].

Introduction: Bibliometric measures variables from the scientific literature that are described quantitatively by means of statistical analysis; this tool seeks to demonstrate the impact of hematopoietic stem cell transplants in the literature throughout the last 45 years. Objective: To describe the indexed medical literature in MEDLINE from 1970 to 2015 on hematopoietic stem cell transplants. Methodology: A search of the MEDLINE database through GoPubMed and Fabumed was performed. The search strategy was: Hematopoietic Stem Cell Transplantation [Majr] and 1970:2015 [dp]. The variables analyzed were the number of publications per year, journals, countries and percentage of publications on hematopoietic stem cell transplants. Results: 23,295 references were recovered on hematopoietic stem cell transplants. 1,844 different journals were identified, the largest number of publications was found in Bone Marrow Transplantation with 2,443 publications, followed by Blood with 1,375 and Biology of Bone Marrow Transplantation with 1,319 references. The United States was the country with the highest number of publications with 7,491 (32.15%), in Latin America 324 (1.39%) were published. The most researched descriptors of literature related to the topic were: Transplantation of hematopoietic stem cells with 23,345 publications, humans with 22,019 and stem cells with 17,564. Conclusions: The publications on hematopoietic stem cell transplants have increased progressively during the 45 years studied. The developed countries are the ones that have done more research on the subject, in contrast to the number of publications in total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. A Bibliometric Study: 45 Years of Biomedical Literature in Hematopoietic Stem Cell Transplantation. MedUNAB 2017-2018; 20(3): 319-326].

Introdução: A bibliometria mede variáveis da literatura científica que são descritas quantitativamente por meio de análise estatística; esta ferramenta procura demonstrar o impacto dos transplantes de células estaminais hematopoiéticas na literatura dos últimos 45 anos. Objetivo: Descrição da literatura médica indexada em MEDLINE de 1970 a 2015 em transplantes de células-tronco hematopoiéticas. Metodologia: uma pesquisa do banco de dados MEDLINE foi realizada através do GoPubMed e Fabumed. Aestratégia de busca foi: "Transplante de células estaminais hematopoiéticas" [Majr] AND "1970: 2015" [dp]. As variáveis analisadas foram o número de publicações por ano, periódicos, países e porcentagem de publicações sobre transplantes de células estaminais hematopoiéticas. Resultados: Foram recuperadas 23,295 referências, em transplantes de células estaminais hematopoiéticas. Identificamos 1,844 periódicos diferentes; o maior número de publicações foi encontrado no Transplante de medula óssea com 2,443 publicações, seguido de sangue com 1,375 e Biologia do transplante de medula óssea com 1,319 referências. Os Estados Unidos foi o país com maior número de publicações com 7,491 (32.15%); na América Latina, foram publicados 324 (1.39%). Os textos mais pesquisados da literatura relacionados com o tema foram: Transplante de células-tronco hematopoiéticas com 23,345 publicações, humanos com 22,019 e células-tronco com 17,564. Conclusões: As publicações sobre transplantes de células estaminais hematopoiéticas aumentaram progressivamente durante os 45 anos estudados. Os países desenvolvidos são os que fizeram mais pesquisas sobre o assunto, em contraste com o número de publicações no total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. Estudo bibliométrico: 45 anos de literatura biomédica em transplante de células-tronco hematopoiéticas. MedUNAB 2017-2018; 20(3): 319-326].

Espiritualidade e religiosidade em mães de crianças com câncer hematológico / Spirituality and religiosity in mothers of children with hematologic cancer / Espiritualidad y religiosidad en madres de niños con cáncer hematológico

Espiritualidade e religiosidade constituem fontes significativas de suporte emocional e social para familiares de crianças gravemente doentes, sobretudo no caso de doenças potencialmente terminais. O transplante de células-tronco hematopoiéticas (TCTH) é um dos tratamentos mais arrojados e promissores que surgiram nas últimas décadas para doenças onco-hematológicas. Trata-se de procedimento altamente invasivo e que envolve risco de morte em decorrência de seus efeitos adversos. Por isso, exige o envolvimento intenso de um cuidador familiar durante todas as suas etapas, o que expõe esse membro da família a estressores contínuos. O objetivo deste estudo foi investigar o sentido atribuído à espiritualidade e religiosidade por mães de crianças com câncer hematológico submetidas ao transplante de células-tronco hematopoéticas.Trata-se de uma pesquisa qualitativa, de delineamento descritivo-exploratório, com fundamentação fenomenológica. Foram entrevistadas dez mães. As entrevistas individuais foram audio gravadas e, posteriormente, transcritas e submetidas à análise compreensiva dos relatos. Espiritualidade e religiosidade emergiram nas falas das participantes, coloridas pelas diferentes crenças religiosas professadas, como fonte de apoio e alento para a cuidadora familiar, auxiliando-a a suportar as adversidades inerentes à situação de ser acompanhante de paciente submetido a procedimento de alto risco. Os resultados corroboram a importância da religiosidade e da espiritualidade como recursos de enfrentamento.

Spirituality and religiosity are important sources of emotional and social support for families of severely ill children, specially when it comes to potentially terminal illnesses. Hematopoietic stem cell transplantation is one of the most daring and promising alternatives that have emerged in the last decades to treat onco-hematological diseases. It is a highly invasive procedure and involves risk of death due to its adverse effects, therefore, it requires close involvement of a family caregiver during allof its stages, which exposes this family member to continuous stressors. The goal of this study was to investigate the meaning attributed to spirituality and religiosity by mothers of hematologic cancer patients undergoing hematopoietic stem cell transplantation. This is a qualitative research, with a descriptive-exploratory design and a phenomenological fundamentation. Ten mothers whose children had undergone hematopoietic stem cell tranplantation were interviewed. Individual interviews were audio-taped and later transcribed and subjected to the comprehensive analysis of the reports. Spirituality and religiosity emerged from the speeches of the participants colored by different professed religious beliefs as a source of support and encouragement for familycaregivers, helping them to deal with the adverse situation of being companion of a patient undergoing a high-risk procedure. Results corroborated that spirituality and religiosity are important coping resources.

Espiritualidad y religiosidad constituyen una importante fuente de apoyo emocional y social para las familias de niños gravemente enfermos, especialmente en lo que se refiere a enfermedades potencialmente terminales. El trasplante de células madre hematopoyéticas es uno de los tratamientos más audaces y más prometedores que han surgido en las últimas décadas para enfermedades onco-hematológicas. Es un procedimiento altamente invasivo que implica riesgo de muerte debido a sus efectos adversos. Por lo tanto, se requiere la participación activa de un cuidador familiar durante todas sus fases, lo que expone a este miembro de la familia a continuos factores de estrés. El objetivo de este estudio fue investigar el significado dado a la espiritualidad y la religiosidad de las madres de niños con cáncer hematológico sometidos a trasplante de células madre hematopoyéticas. Se trata de un estudio cualitativo, con diseño descriptivo y exploratorio y fundamentación fenomenológica. Se entrevistaron a diez madres. Las entrevistas individuales fueron grabadas en audio y posteriormente transcritas y sometidas a análisis comprehensiva de los informes. La espiritualidad y la religiosidad surgieron en los discursos de las participantes, coloreado por las diferentes creencias religiosas profesas como fuente de apoyo y aliento a las madres cuidadoras, lo que ayuda a soportar las dificultades inherentes a la situación de ser compañera de un paciente sometido a un procedimiento de alto riesgo. Los resultados confirman la importancia de la espiritualidad y la religiosidad como recurso de afrontamiento

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

Trasplante autológo de células madre hematopoyéticas en pacientes con diagnóstico de neuroblastoma de alto riesgo en la Fundación Valle del Lili, Cali - Colombia / Autologous Haematopoietic Stem-cell Transplantation in Patients with High Risk Neuroblastoma in the Valle del Lili Foundation Hospital, Cali, Colombia

Resumen Objetivo: Describir la experiencia en el manejo de los pacientes con diagnóstico de neuroblastoma de alto riesgo manejados con trasplante autólogo de células madre hematopoyéticas en la Fundación Valle de Lili. Pacientes y métodos: Estudio descriptivo, tipo serie de casos de pacientes con diagnóstico de neuroblastoma de alto riesgo que recibieron trasplante autólogo de células madre hematopoyéticas entre 2001 y 2015. Los desenlaces de este estudio fueron: supervivencia global; supervivencia libre de evento; tiempo de injerto de plaquetas y neutrófilos, e incidencia acumulada de enfermedad veno oclusiva. Se realizó un análisis estadístico descriptivo para todas las variables consideradas en el análisis y para subgrupos seleccionados. El análisis de supervivencia se hizo con el método Kaplan-Meier. Resultados: Entre 2001 y 2015 quince pacientes con diagnóstico de neuroblastoma recibieron trasplante autólogo de células madre hematopoyéticas. La supervivencia globala3y5anos fue del 55% y la supervivencia libre de evento fue del 47%, donde 14 pacientes injertaron neutrófi los entre el día8y19 postrasplante e injerto de plaquetas entre los 9 y 91 días y 2 pacientes desarrollaron enfermedad venooclusiva hepatica como toxicidad a los fármacos quimioterapéuticos de acondicionamiento. Al momento del último seguimiento 10 pacientes permanecen vivos, de los cuales 8 no presentan evidencia clínica y/o paraclínica de la enfermedad. De los 5 pacientes que fallecieron, 2 fue por toxicidad al trasplante en los primeros 100 díasy3por progresión de la enfermedad. Conclusión: El trasplante autólogo de células madre hematopoyéticas es una alternativa facti ble como tratamiento en nuestro medio para pacientes con diagnóstico de neuroblastoma de alto riesgo, el cual ha contribuido a mejorar la supervivencia en este grupo de pacientes.

Abstract Objective: Describe the experience in the management of patients diagnosed with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation at the Valle de Lili Foundation Hospital. Patients and Methods: A series of cases of patients with a diagnosis of high-risk neuroblastoma who received an autologous haematopoietic stem cell transplantation between 2001 and 2015. The endpoints of this study were: overall survival, event-free survival, platelet and neutrophil graft time and the cumulative incidence of venous-occlusive disease. A descriptive statistical analysis was performed for all the variables considered in the analysis and for the selected subgroups. Survival analysis was performed using the Kaplan-Meier method. Results: A total of 15 patients diagnosed with high risk neuroblastoma received an autologous haematopoietic stem cell transplantation between 2001 and 2015. Overall survival at 3 and 5 years was 55%, and the event-free survival was 47%. 14/15 patients grafted Neutrophils grafted between day 8 and 19 post-transplant in 14/15 patients, with platelet graft between days 9 and 91 days. Hepatic venous-occlusive disease was observed in 2/15 patients as toxicity to conditioning chemotherapeutic drugs. At the time of the last follow-up, 10/15 patients remained alive, 8 of whom had no clinical and/or para-clinical evidence of the disease. Of the 5/15 patients that died, 2 were due to transplant toxicity in the first 100 days, and 3 due to disease progression. Conclusion: We conclude that autologous haematopoietic stem cell transplantation is a viable alternative as a treatment in our setting for patients with high-risk neuroblastoma, and has contributed to improve survival in this group of patients.

Comparison of Reprogramming Methods for Generation of Induced-Oligodendrocyte Precursor Cells

Direct conversion by trans-differentiation is of growing interest in cell therapy for incurable diseases. The efficiency of cell reprogramming and functionality of converted cells are important considerations in cell transplantation therapy. Here, we compared two representative protocols for the generation of induced-oligodendrocyte progenitor cells (iOPCs) from mouse and rat fibroblasts. Then, we showed that induction of Nkx6.2, Olig2, and Sox10 (NOS) was more effective in mouse fibroblasts and that induction of Olig2, Sox10, and Zfp536 (OSZ) was more effective at reprogramming iOPCs from rat fibroblasts. However, OSZ-iOPCs did not show greater proliferation than NOS-induced cells. Because the efficiency of iOPCs generation appears to differ between cell species depending on transcription factors and culture conditions, it is important to select appropriate methods for efficient reprogramming.

Comparison of Reprogramming Methods for Generation of Induced-Oligodendrocyte Precursor Cells

Direct conversion by trans-differentiation is of growing interest in cell therapy for incurable diseases. The efficiency of cell reprogramming and functionality of converted cells are important considerations in cell transplantation therapy. Here, we compared two representative protocols for the generation of induced-oligodendrocyte progenitor cells (iOPCs) from mouse and rat fibroblasts. Then, we showed that induction of Nkx6.2, Olig2, and Sox10 (NOS) was more effective in mouse fibroblasts and that induction of Olig2, Sox10, and Zfp536 (OSZ) was more effective at reprogramming iOPCs from rat fibroblasts. However, OSZ-iOPCs did not show greater proliferation than NOS-induced cells. Because the efficiency of iOPCs generation appears to differ between cell species depending on transcription factors and culture conditions, it is important to select appropriate methods for efficient reprogramming.