Treatment outcome at the pediatric stem cell transplantation center in Syria: A single-center experience.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach known for its high success rates in treating various hematologic malignancies, hemoglobinopathies, immune deficiencies, and other disorders. Notably, pediatric HSCT commenced in Syria in 2021 amidst the prevailing crisis. This study aims to assess the demographic and clinical profiles of pediatric patients who underwent stem cell transplantation and to analyze treatment outcomes at Syria's inaugural pediatric HSCT center. METHODS: This study is a single-center retrospective analysis of 25 pediatric patients who underwent HSCT underage of 14 years in the National Stem Cell Center (HAYAT) in Damascus within the period 2021-2023. The databases were created based on data that were collected from patient medical records. RESULTS: In autologous patients, transplant-related mortality (TRM) was 0%, with 4 (57%) experiencing disease relapse, resulting in the death of one patient. Additionally, 3 (42.8%) of patients remain alive under second-line management. The overall survival rate was 6 (85.7%), and the disease-free survival rate was 16 (88%). In allogeneic patients, TRM was 5.5% (1/18). One allogeneic patient experienced disease relapse and subsequently died. The overall survival rate and disease-free survival rate were 16 (88%). CONCLUSIONS: The objective of this study was to assess the outcomes of pediatric HSCT patients who have undergone transplantation thus far. Given the recent initiation of pediatric stem cell transplantation in Syria, our dataset provides a basis for comparison with international hematopoietic stem cell transplantation centers regarding treatment complications and outcomes, notwithstanding the challenges and crises faced within our country.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. METHODS: A pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). RESULTS: The primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60' (p = 0.07) and 90' (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. CONCLUSION: Intraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women: a randomized, controlled trial.

Intrauterine adhesion is a major cause of female reproductive disorders. Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth, no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far. To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate, we conducted this randomized controlled clinical trial. Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter (control group) from February 2016 to January 2020. The per-protocol analysis included 140 participants: 72 in bone marrow stem cells-scaffold group and 68 in control group. The ongoing pregnancy occurred in 45/72 (62.5%) participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group (28/68, 41.2%) (RR=1.52, 95%CI 1.08-2.12, P=0.012). The situation was similar in live birth rate (bone marrow stem cells-scaffold group 56.9% (41/72) vs. control group 38.2% (26/68), RR=1.49, 95%CI 1.04-2.14, P=0.027). Compared with control group, participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis. The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed. In conclusion, transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates, and this therapy was relatively safe.

Insuficiencia cardiaca secundaria a amiloidosis AL: diagnóstico y tratamiento / Heart failure secondary to amyloidosis AL: diagnosis and treatment

Resumen La amiloidosis por depósito de cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuen te y subdiagnosticada. El mejor tratamiento disponible al momento es el trasplante autólogo de médula ósea (TMO). El compromiso cardíaco es el principal determi nante pronóstico en esta patología y en ocasiones un impedimento para recibir el TMO. Se presenta el caso de un varón de 44 años que consultó por signos y síntomas de insuficiencia cardiaca (IC) con biomarcadores cardia cos elevados. Se realizó un ecocardiograma transtorácico donde se objetivó aumento de espesores parietales con hipoquinesia global y fracción de eyección deteriorada en grado leve (50%). El paciente se internó en unidad coronaria para balance negativo y para estudio etiológico del cuadro. Ante la sospecha de enfermedad infiltrativa, se solicitaron un centellograma óseo con pirofosfato y cadenas livianas libres en suero. El centellograma óseo resultó no sugestivo para amiloidosis por transtiretina y las cadenas livianas libres mostraron una relación me nor a 0.26 con predominio lambda. Se realizó una biopsia de encía que confirmó el diagnóstico de amiloidosis AL. Posterior al diagnóstico comenzó tratamiento qui mioterápico específico con Ciclofosfamida, Bortezomib y Dexametasona (esquema CYBORD) y Daratumumab. Evolucionó con IC refractaria por lo que ingresó a lista de trasplante cardiaco, recibiendo el mismo al poco tiempo con buena evolución. Esto permitió reiniciar el esquema quimioterápico y en segundo término finalmente recibir el TMO, con buena evolución.

Abstract Light chain amyloidosis (AL) is a rare and underdi agnosed disease. The best treatment available is au tologous bone marrow transplantation (BMT). Cardiac involvement is the main prognostic determinant in this pathology and sometimes an impediment to re ceive BMT. We present a clinical case of a 44-year-old who consulted for signs and symptoms of heart failure (HF) with elevated cardiac biomarkers. A transthoracic echocardiogram showed increased wall thickness with global hypokinesia and mildly impaired ejection fraction (50%). The patient was admitted to the coronary unit for treatment with diuretics and for etiological study of the condition. In view of the suspicion of infiltrative disease, a bone scintigraphy with pyrophosphate and free light chains in serum were requested. The bone scintigraphy was not suggestive of transthyretin amyloidosis and the free light chains showed a ratio of less than 0.26 with lambda predominance. A gum biopsy was per formed and confirmed the diagnosis of AL amyloidosis. After diagnosis, specific chemotherapy treatment with Cyclophosphamide, Bortezomib and Dexamethasone (CYBORD scheme) and Daratumumab was started. He evolved with refractory HF so it was decided to admit him to the cardiac transplantation list, receiving the same soon after, with good evolution. This allowed the patient to restart the chemotherapy regimen and finally receive BMT, with good evolution.

Analysis of the efficacy of drilling decompression autologous bone marrow and allogeneic bone grafting in the treatment of HIV-positive patients with early osteonecrosis of the femoral head.

OBJECTIVE: To investigate the efficacy of treating patients with HIV-positive osteonecrosis of the femoral head using drilled decompression autologous bone marrow and allogeneic bone grafting. METHODS: 40 patients (44 hips) with early osteonecrosis of the femoral head treated by drilling decompression autologous bone marrow and allogeneic bone grafting since October 2015 were retrospectively analyzed, among which 20 patients (24 hips) were HIV-positive patients with early osteonecrosis of the femoral head, 16 males and 4 females, age 22-43 years, average 39.6 ± 10.18 years, and 20 patients (20 hips) in the same period HIV-negative early osteonecrosis of the femoral head patients, 13 males and 7 females, aged 48-78 years, mean 63.50 ± 7.94 years were negative controls. General information including ARCO stage, Harris score, VAS score, hematological indexes including CD4+ T lymphocyte count, and HIV viral load was recorded for all patients before surgery. All patients were operated on by drilling and decompression of the necrotic area, harvesting autologous iliac bone marrow with allogeneic bone, and bone grafting through the decompression channel. The patients were followed up regularly at 6, 12, and 24 months after surgery and annually thereafter, and the repair of the necrotic femoral head was observed by reviewing the frontal and lateral X-ray, CT or MRI of the hip joint, and the complications and functional recovery of the hip joint was counted and compared between the two groups. RESULTS: All patients were followed up, and the ARCO stages in the HIV-positive group were stage I 2 hips, stage IIA 6 hips, stage IIB 8 hips, stage IIC 6 hips, and stage III 2 hips, with a follow-up time of 12 to 60 months and a mean of 24.6 months. In the negative control group, there were 3 hips in ARCO stage I, 7 hips in stage IIA, 5 hips in stage IIB, 3 hips in stage IIC, and 2 hips in stage III, and the follow-up time ranged from 13 to 62 months, with an average of 24.8 months. The Harris score and VAS score of the hip in both groups improved significantly at 6 months postoperatively compared with those before surgery (P < 0.001). The difference between the Harris score of the hip in the positive group at 24 months postoperatively compared with that at 6 months postoperatively was statistically significant, but the VAS score at 24 months postoperatively compared with that at 6 months postoperatively was not statistically significant. In the negative group, there was no statistically significant difference in the Harris score and VAS score of the hip at 24 months postoperatively compared with those at 6 months postoperatively. In the positive group, there was a trend of continuous increase in hip BMD from the beginning of the postoperative period (P < 0.001). There was no statistically significant difference between the negative group and the positive group at the 24 months postoperatively follow-up except for the Harris score, which was statistically significant (P < 0.001), and the VAS score, which was statistically insignificant. At the 24 months postoperatively follow-up, patients in both groups had good recovery of hip function, and no complications such as vascular and nerve injury and fracture occurred during the perioperative period and follow-up period, and no complications related to incisional infection and pulmonary infection occurred during hospitalization. CONCLUSION: The treatment of early HIV-positive osteonecrosis of the femoral head patients with autologous bone marrow and allogeneic bone grafting by drilling and decompression to remove the tissue in the necrotic area of the femoral head can effectively stop the process of osteonecrosis of the femoral head and promoting femoral head repair in HIV-positive patients is a safe and effective method for treating HIV-positive patients with early osteonecrosis of the femoral head, and can effectively delay or postpone total hip replacement in patients.

Autologous bone marrow infusion via portal vein combined with splenectomy for decompensated liver cirrhosis: A retrospective study.

BACKGROUND: In a previous study, autologous bone marrow infusion (ABMI) was performed in patients with decompensated liver cirrhosis (DLC) and acquired immunodeficiency syndrome and achieved good results, but whether splenectomy affected outcome was unclear. AIM: To investigate the efficacy of ABMI combined with splenectomy for treatment of DLC. METHODS: Eighty-three patients with DLC were divided into an intervention group (43 cases) and control group (40 cases) according to whether splenectomy was performed. The control group was treated with ABMI through the right omental vein, and the intervention group was additionally treated with splenectomy. RESULTS: After ABMI, the prothrombin time, serum total bilirubin levels, ascites volume and model for end-stage liver disease score in both groups were significantly lower, while the albumin levels were significantly higher than before ABMI (P < 0.01), but there were no significant differences between the groups (P > 0.05). After ABMI, the white blood cell and platelets counts in both groups were significantly higher than before ABMI (P < 0.01), and the counts in the intervention group were significantly higher than in the control group (P < 0.01). After ABMI the CD4+ and CD8+ T cell counts in both groups were significantly higher than before ABMI (P < 0.01). The CD8+ T cell counts in the intervention group increased continuously and the increase had a shorter duration compared with control group. CONCLUSION: ABMI through the portal vein in patients with DLC can significantly improve liver synthetic and secretory functions, and splenectomy promotes improvement of bone marrow hematopoietic and cellular immune functions.

[Heart failure secondary to amyloidosis AL: diagnosis and treatment]. / Insuficiencia cardiaca secundaria a amiloidosis AL: diagnóstico y tratamiento.

Light chain amyloidosis (AL) is a rare and underdiagnosed disease. The best treatment available is autologous bone marrow transplantation (BMT). Cardiac involvement is the main prognostic determinant in this pathology and sometimes an impediment to receive BMT. We present a clinical case of a 44-year-old who consulted for signs and symptoms of heart failure (HF) with elevated cardiac biomarkers. A transthoracic echocardiogram showed increased wall thickness with global hypokinesia and mildly impaired ejection fraction (50%). The patient was admitted to the coronary unit for treatment with diuretics and for etiological study of the condition. In view of the suspicion of infiltrative disease, a bone scintigraphy with pyrophosphate and free light chains in serum were requested. The bone scintigraphy was not suggestive of transthyretin amyloidosis and the free light chains showed a ratio of less than 0.26 with lambda predominance. A gum biopsy was performed and confirmed the diagnosis of AL amyloidosis. After diagnosis, specific chemotherapy treatment with Cyclophosphamide, Bortezomib and Dexamethasone (CYBORD scheme) and Daratumumab was started. He evolved with refractory HF so it was decided to admit him to the cardiac transplantation list, receiving the same soon after, with good evolution. This allowed the patient to restart the chemotherapy regimen and finally receive BMT, with good evolution.

La amiloidosis por depósito de cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente y subdiagnosticada. El mejor tratamiento disponible al momento es el trasplante autólogo de médula ósea (TMO). El compromiso cardíaco es el principal determinante pronóstico en esta patología y en ocasiones un impedimento para recibir el TMO. Se presenta el caso de un varón de 44 años que consultó por signos y síntomas de insuficiencia cardiaca (IC) con biomarcadores cardiacos elevados. Se realizó un ecocardiograma transtorácico donde se objetivó aumento de espesores parietales con hipoquinesia global y fracción de eyección deteriorada en grado leve (50%). El paciente se internó en unidad coronaria para balance negativo y para estudio etiológico del cuadro. Ante la sospecha de enfermedad infiltrativa, se solicitaron un centellograma óseo con pirofosfato y cadenas livianas libres en suero. El centellograma óseo resultó no sugestivo para amiloidosis por transtiretina y las cadenas livianas libres mostraron una relación menor a 0.26 con predominio lambda. Se realizó una biopsia de encía que confirmó el diagnóstico de amiloidosis AL. Posterior al diagnóstico comenzó tratamiento quimioterápico específico con Ciclofosfamida, Bortezomib y Dexametasona (esquema CYBORD) y Daratumumab. Evolucionó con IC refractaria por lo que ingresó a lista de trasplante cardiaco, recibiendo el mismo al poco tiempo con buena evolución. Esto permitió reiniciar el esquema quimioterápico y en segundo término finalmente recibir el TMO, con buena evolución.

Cytokine Dynamics in Autism: Analysis of BMAC Therapy Outcomes.

Autism spectrum disorder (ASD) has recently been linked to neuroinflammation and an aberrant immune response within the central nervous system. The intricate relationship between immune response and ASD remains elusive, with a gap in understanding the connection between specific immune mechanisms and neural manifestations in autism. In this study, we employed a comprehensive statistical approach, fusing both overarching and granular methods to examine the concentration of 16 cytokines in the cerebrospinal fluid (CSF) across each autologous bone marrow aspirate concentrate (BMAC) intrathecal administration in 63 male and 17 female autism patients. Following a six-month period post the third administration, patients were stratified into three categories based on clinical improvement: Group 1- no/mild (28 subjects), Group 2-moderate (16 subjects), and Group 3-major improvement (15 subjects). Our integrated analysis revealed pronounced disparities in CSF cytokine patterns and clinical outcomes in autism subjects pre- and post-BMAC transplantation. Crucially, our results suggest that these cytokine profiles hold promise as predictive markers, pinpointing ASD individuals who might not exhibit notable clinical amelioration post-BMAC therapy.

A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI. METHODS: We performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford's classification) and a transcutaneous oxygen pressure (TcPO2) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 106 ± 2.984 × 106 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 106 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford's classification, (ii) TcPO2, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire). RESULTS: No adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford's classification, a significant increase in TcPO2 values‬, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation. CONCLUSIONS: Our results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444).

A case report: The first show phenomenon in the treatment of spinal cord injury with Regentime procedure using autologous bone marrow-derived stem cells.

Key Clinical Message: Promising outcomes are shown in this case report using the Regentime procedure and autologous stem cells to treat spinal cord injury. The observed "First Show Phenomenon" provides valuable insights into the therapy's potential for spinal cord injury. Abstract: This case report demonstrates "the first show phenomenon" following Regentime stem cell therapy applied to a spinal cord injury patient. A 40-year-old gentleman sustained a ballistic injury at the level of T9, resulting in complete bilateral motor and sensory loss from T9 and below. He was treated with autologous bone marrow-derived mononuclear stem cells injected into his spinal canal 2.5 years after his injury. Follow-up during the first-week posttransplantation showed early symptom improvement termed "the first show phenomenon." He regained sensation to light touch in his lower limbs by the end of week 1 and reported no serious implications or complications.

Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida.

BACKGROUND: To evaluate the safety and efficacy of autologous bone marrow mononuclear cell (BMMNC) infusion in the management of neurological sequelae in children with spina bifida (SB). METHODS: BMMNCs were harvested from bilateral anterior iliac crests. Two intrathecal BMMNC administrations were performed with an interval of 6 months. The measurements of outcomes included clinical assessments, cystomanometry and rectomanometry. RESULTS: Eleven children with SB underwent autologous BMMNC infusions from 2016 to 2020. There were no severe adverse events during the study period. The number of patients requiring assistance to expel stools decreased from 11 before cell infusion to 3 after the second cell infusion. The number of patients who had urine leakage decreased from 9 patients at baseline to 3 patients after the second BMMNC infusion. The mean bladder capacity increased from 127.7 ± 59.2 ml at baseline to 136.3 ± 54.8 ml at six months and to 158.3 ± 56.2 ml at 12 months after BMMNC infusions. Detrusor pressure (pdet) decreased from 32.4 ± 22.0 cm H2O at baseline to 21.9 ± 11.8 cm H2O after 12 months of follow-up. At baseline, six patients could walk independently. After the 2nd infusion, eight patients could walk independently. CONCLUSION: Intrathecal infusions of autologous bone marrow mononuclear cells are safe and may improve bowel, bladder, and motor function in children with SB. TRIAL REGISTRATION: NCT, NCT05472428. Registered July 25, 2022- Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05472428 .

Autologous bone marrow-derived nucleated cell (aBMNC) transplantation improves endometrial function in patients with refractory Asherman's syndrome or with thin and dysfunctional endometrium.

PURPOSE: The purpose was to evaluate the effect of intrauterine injection of aBMNC on the endometrial function in patients with refractory Asherman's syndrome (AS) and/or thin and dysfunctional endometrium (TE). STUDY DESIGN: This is a prospective, experimental, non-controlled study MATERIAL AND METHODS: The study was carried out between December 2018 and December 2020 on 20 patients, who were of age < 45 years and had oligo/amenorrhea and primary infertility due to refractory AS and/or TE. One hundred ml BM was extracted. aBMNC cells were separated according to generic volume reduction protocol by using the Cell Separation System SEPAX S-100 table top centrifuge system. We have evaluated CD34+, mononuclear cell (MNC), and total nucleated cell (TNC) counts. The transplantation aBMNC was performed by two intrauterine injections at an interval of one week, transvaginally into the endometrial-myometrial junction by an ovum aspiration needle. Midcyclic endometrial thickness (ET) and gestations after transplantation were evaluated. RESULTS: The mean TNC, MNC, and CD34+ cells were 11.55 ± 4.7 × 108, 3.85 ± 2.01 × 108, and 7.00 ± 2.88 × 106 at first injection, respectively, and 6.85 ± 2.67 × 108, 2.04 ± 1.11 × 108, and 3.44 ± 1.31 × 106 at second injection, respectively. The maximum posttransplantation ET was significantly higher than the maximum pretransplantation ET: 2.97 ± 0.48 vs. 5.76 ± 1.19 (mean ± standard deviation, p < 0.01). Twelve patients had frozen-thaw embryo transfers after the study. In 42% (n = 5 of 12) of the patients, pregnancy was achieved. One of the five patients delivered a healthy baby at term. CONCLUSIONS: Autologous BMNC transplantation may contribute to endometrial function in patients with AS and/or TE.

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

OBJECTIVE: We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. METHODS: Eight male patients (age 62 ± 2.4 years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. RESULTS: No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6 months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. CONCLUSIONS: Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.

Comparison Between Concentrated Autologous Bone Marrow Aspirate Transplantation as a Hip Preserving Surgery and Natural Course in Idiopathic Osteonecrosis of the Femoral Head.

Purpose The purpose is to compare the therapeutic efficacy of concentrated autologous bone marrow aspirate transplantation (CABMAT) with that of observation alone for osteonecrosis of the femoral head (ONFH). Methods This single-center study included patients with idiopathic ONFH that were either treated with CABMAT (CABMAT group) or managed through observation alone (observation group) over a >2-year follow-up period. The Japanese Investigation Committee classification was used to diagnose and classify ONFH. The collapse rates for stages 1 and 2 ONFH (i.e., pre-collapse stages) and the THA conversion rates were compared between the CABMAT and observation groups. Results The CABMAT and observation groups comprised 232 (mean follow-up: 8.2 years) and 106 (mean follow-up: 6.0 years) patients, respectively. No significant intergroup differences were noted in the stages, types, and associated factors of ONFH. The collapse rates for pre-collapse stages in the CABMAT and observation groups were 67.1% and 65.3%, respectively. For stage 1, the collapse rates were significantly lower in the observation group than in the CABMAT group (p<0.05). The overall THA conversion rates in the CABMAT and observation groups were 24.3% and 41.5%, respectively (p<0.0001). For ONFH of stages 3A and 3B (collapse stages), the THA conversion rates were significantly lower in the CABMAT group (p<0.05). Conclusion Collapse rates were significantly higher for stage 1 ONFH; for collapse stages, the THA conversion rates were significantly lower in the CABMAT group than in the observation group. Therefore, observation and CABMAT are recommended for ONFH of stage 1 and for ONFH of higher stages, respectively.

Autologous bone marrow aspirate concentrate (BMAC) for treatment of keratocystic odontogenic tumour (KCOT)-a case report.

Management of keratocystic odontogenic tumor (KCOT) has always remained a conundrum due to its aggressive behavior, indicating wide resection. Achieving an esthetically and functionally acceptable reconstruction remains a challenge. Herein, we present a novel and less invasive technique for the treatment of KCOT. A 55-year-old female presenting with pain in the lower jaw for the past 3 months was diagnosed with a large KCOT extending from 35 to 47 region. CT images revealed buccal and lingual cortical bone erosion. Management was done in two stages: cyst curettage and chemical cauterization, followed by application of Bone Marrow Aspirate Concentrate (BMAC) with a delay of two months, to increase the thickness of eroded cortical bone. On follow-up at one year, ossification of the defect was observed. BMAC is a cocktail of mesenchymal stromal cells, hematopoietic stem cells, fibroblasts, mononuclear cells, macrophages, endothelial cells, progenitor cells, growth factors and cytokines. BMAC cocktail provide an anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory environment. Autologous platelet rich plasma provides various growth factors (TGF-ß, PDGF, EGF, HGF, NGF, IGF-1) and cytokines. Addition of PRP in BMAC cocktail enhance the regeneration of tissues, where PRP act as a functional regenerative scaffold for cell integration, proliferation, and differentiation that can expedite macroscale musculoskeletal tissue healing. Autologous BMAC with corticocancellous bone acts as an osteoconductive scaffold capable of regenerating the large bone defect created by the curettage of KCOT.

Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes.

Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.

Combining autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression improves short-term outcomes in early avascular necrosis of the femoral head: a prospective, randomized, comparative study.

BACKGROUND: Treatment of avascular necrosis of the femoral head (ANFH) in young patients remains a clinical challenge. A current controversy is whether hip-preserving surgery results in better outcomes. The adverse effects of hip-preserving surgery are associated with the fill material for the necrotic areas. This study aims to evaluate the early effects of autologous bone marrow buffy coat (BBC) and angioconductive bioceramic rod (ABR) grafting with advanced core decompression (ACD) on early ANFH. METHODS: Forty-four (57 hips) patients with early ANFH from 2015 to 2020 were recruited for this study. They were randomized into two groups: group A received ACD, BBC, and ABR grafting; group B received treatment of ACD with ß-tricalcium phosphate (ß-TCP) granules and ABR grafting. The outcomes were assessed using the Harris Hip Scores (HHS) and survival rate analysis. The follow-up endpoint was defined as conversion to total hip arthroplasty (THA). RESULTS: Forty patients (51 hips) were ultimately included in this study for analysis. Compared with group B, patients in group A had higher postoperative function score (P = 0.032) and postoperative Harris Hip Scores (HHS) (P = 0.041). Kaplan-Meier analysis showed a trend that the survivorship of the femoral head was higher in group A than in group B. CONCLUSION: The short-term follow-up results showed that the autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression is effective in the treatment of early ANFH. TRIAL REGISTRATION: Chictr.org.cn , ChiCTR2000039595. Retrospectively registered on 11 February 2015.

Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration.

Intrauterine adhesions (IUAs) refer to the repair disorder after endometrial injury and may lead to uterine infertility, recurrent miscarriage, abnormal menstrual bleeding, and other obstetric complications. It is a pressing public health issue among women of childbearing age. Presently, there are limited clinical treatments for IUA, and there is no sufficient evidence that these treatment modalities can effectively promote regeneration after severe endometrial injury or improve pregnancy outcome. The inhibitory pathological micro-environment is the main factor hindering the repair of endometrial damaged tissues. To address this, tissue engineering and regenerative medicine have been achieving promising developments. Particularly, biomaterials have been used to load stem cells or therapeutic factors or construct an in situ delivery system as a treatment strategy for endometrial injury repair. This article comprehensively discusses the characteristics of various bio-scaffold materials and their application as stem cell or therapeutic factor delivery systems constructed for uterine tissue regeneration.