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.

Concentrated autologous bone marrow aspirate transplantation versus conservative treatment for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus / Journal of Rural Medicine

Objective: To compare the outcomes of steroid-associated osteonecrosis of the femoral head in patients with systemic lupus erythematosus who underwent conservative treatment and concentrated autologous bone marrow aspirate transplantationMethods: Osteonecrosis of the femoral head was classified according to the Japanese Investigation Committee system. Concentrated autologous bone marrow aspirate transplantation was performed by aspirating the bone marrow from both iliac crests and then transplanting it to the necrotic area after the core decompression. Patients with >2-year follow-up after the concentrated autologous bone marrow aspirate transplantation in our institution (Group I) and those with >2-year follow-up after the first hospital visit in a cooperative institution (Group II) were included in this study. After a randomized matching based on age, sex, type, stage, and etiology, the collapse rate in pre-collapsed stages and total hip arthroplasty conversion rate in all stages were compared between the two groups.Results: After the matching adjustment, 33 pairs of hips were included. Preoperatively, 1, 2, 16, and 14 hips were classified as types A, B, C1, and C2, respectively, and 15, 13, 2, and 3 hips were classified as stages 1, 2, 3A, and 3B, respectively. The collapse rates in the pre-collapsed stages were 68% and 39% in Groups I and II, respectively. Total hip arthroplasty conversion rates were 33% and 45% in Groups I and II, respectively. However, Group I had significantly higher and lower conversion rates in stages 1 and 3, respectively (both P<0.05).Conclusion: Conservative treatment may be preferable in stage 1 hips. In addition, concentrated autologous bone marrow aspirate transplantation may prevent further collapse in stage 3.

Safety of autologous bone marrow mesenchymal stem cells transplantation in proliferative diabetic retinopathy patients / 中华实验眼科杂志

Objective To investigate the safety of autologous bone marrow mesenchymal stem cells (ABMSCs) transplantation into the subretinal space for the treatment of proliferative diabetic retinopathy (PDR). Methods The clinical data of four PDR patients ( four eyes ) who received ABMSCs transplantation into the subretinal space were collected in Army Medical University,Southwest Eye Hospital from March 2014 to December 2015,including 3 males and 1 female;the average age was 55 years old;the average course of diabetes was 10 years, and the blood glucoses were all well controlled before treatment. All the patients underwent conventional ophthalmologic examination,and visual acuity,slit lamp microscope,color fundus photography,fluorescein angiography (FFA) and optical coherence tomography ( OCT) examination were performed at 1 week,1 month,3 months,6 months,9 months and 12 months after surgery. This study protocol was approved by Ethic Committee of Army Medical University,Southwest Eye Hospital (No. 2013-34). Results Four patients diagnosed as PDR were enrolled in this study. All patients were performed ABMSC transplantation,and no one felt discomfort after treatment. FFA and OCT showed that the transplanted cells were present in the subretinal space until 1 month after transplantation. The macular edema of one patient diagnosed as macular edema preoperatively was relived gradually after transplantation,and the effects lasted 3 months after transplantation. The preoperative best corrected visual acuity (BCVA) of the two patients were improved from hand movement and finger counting to 20/20 ( 84 ETDRS) and 20/200 ( 38 ETDRS) after transplantation,respectively,and the visual acuities of the other two eyes were both stable. All patients underwent panretinal photocoagulatio 3 months after transplantation, and the follow-up treatment complied with the routine of post-vitrectomy for DR, no complications occurred during the follow-up period. Conclusions Subretinal transplantation of ABMSCs for PDR is safe. The transplanted cells show local anti-inflammatory effect,and no effect on cell proliferation or circulatory improvement are observed.

Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis

Stem cell therapy, an evolving, progressive field of therapeutics has shown several successes in areas where classic treatments failed to prevent or stop disability. Starting in 2009, twenty two sequential patients with progressive Multiple Sclerosis (MS) courses were treated with Autologous Bone Marrow Mononuclear stem cells (BM-MNSCs). The cells were given both intravenously and intrathecally. Using the Expanded Disability Status Scale (EDSS) score for evaluation, our data indicates that the majority of the patients benefited on the average one point on the scale. This paper adds to the body of evidence suggesting the safety and efficacy of autologous BM-MNSCs in the treatment of MS and awaits validation through larger, randomized studies.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial.

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 108 (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Union Rates of Autologous Bone Marrow, Local Autobone and Biphasic Calcium Phosphate Mixed Graft in Lumbar Posterolateral Fusion

STUDY DESIGN: A retrospective study. OBJECTIVES: We examined union rates and clinical outcomes to evaluate the efficacy of using autologous bone marrow along with a local autobone and biphasic calcium phosphate mixed graft with posterolateral fusion in spinal stenosis and spondylolisthesis. SUMMARY OF LITERATURE REVIEW: In lumbar posterolateral fusion, union rates of biphasic calcium phosphate and local autobone mixed graft are low compared to union rates of autogenous iliac bone graft. MATERIALS AND METHODS: Among the patients who had lumbar posterolateral fusion with autologous bone marrow along with local autobone and biphasic calcium phosphate mixed graft between February 2013 and January 2014, we analyzed 40 patients who were available for at least one year of follow-up. There were 22 cases with spinal stenosis and 18 cases with spondylolisthesis. Bone fusion was determined along with the fusion rates based on Lenke's criteria (citation). All patients were evaluated postoperatively at one year, using 3D CT. and the clinical outcomes were assessed using Kim's method (citation). RESULTS: In spinal stenosis, bone union was observed in 19 cases out of 22 (86.4%), and in case of spondylolisthesis, bone union was observed in 16 cases out of 18 (88.9%). In spinal stenosis, the clinical outcomes were: 2 excellent, 16 good, 3 fair, and 1 poor; in other words 18 cases (81.8%) displayed good or excellent outcomes. In spondylolisthesis, 2 excellent, 12 good, 4 fair and 0 poor; in other words, 14 cases (77.8%) showed good or superior outcomes. CONCLUSIONS: Posterolateral fusion using autologous bone marrow along with a local autobone and biphasic calcium phosphate mixed graft showed similar bone fusion rates to using autogenous iliac bone graft. Therefore, this method could serve as an alternative to using autogenous iliac bone graft in posterior lumbar fusion.

Clinical study on optimization scheme of autologous bone marrow stem cell transplantation for decompensated cirrhosis / 中国生化药物杂志

Objective To compare the therapeutic effects of bone marrow stem treatment by different bone marrow mobilization,distinct separation methods or cell suspension density, and to explore the optimal treatment plan of autologous bone marrow stem cell transplantation for decompensated cirrhosis.Methods Twenty three patients with decompensated cirrhosis were studied.100 ~200 mL bone marrow from each patient was harvested in aseptic condition, after isolation and purification by density gradient centrifugation,the stem cells were obtained and transplanted into the liver via hepatic artery.The serum glutamic acid alanine aminotransferase (ALT), albumin (ALB), prothrombin time (PT) and total bilirubin (TBIL) were checked before and l, 2, 3 months after therapy respectively,changes in these indicators of each group were compared by different bone marrow mobilization, distinct separation methods, or cell suspension density.Results After transplantation, levels of albumin increased significantly 1, 2, 3 months after treatment compared with baseline(P<0.05).Patients in bone marrow mobilization group obtained higher stem cell density (P<0.05), which had no significant difference in improving liver function ( ALT, TBIL, ALB, PT) compared with non-bone marrow mobilization group.Patients using the kit significantly improved their albumin (3 months after treatment, P<0.05), which had no significant difference in improving liver function (ALT, TBIL, ALB, PT) compared with using ordinary lymphocyte isolation method group.There was no significant difference in improving liver function ( ALT, TBIL, ALB, PT) between lower magnitude stem cell density group(≤1 ×1010/L) and higher magnitude stem cell density group(1 ×1010/L).Conclusion The treatment for decompensated cirrhosis by transplantation of autologous bone nlarrow stem cells is safe and effective, which can significantly increase the level of albumin in patients with decompensated cirrhosis.Preoperative bone marrow mobilization can increase the rate of stem cells obtained, and the method using the kit improves the leves of protein respectively.They are helpful to improve the efficacy.

Aplicação de células-tronco mesenquimais no tratamento de lesões raquimedulares naturalmente adquiridas em cães e em gatos domésticos / Application of mesenchymal stem cells in the treatment of naturally acquired spinal cord injuries in dogs and domestic cats

Mecanismos de lesão e suas consequencias decorrentes de injúria da medula espinhal (IME) envolvem morte neuronal tanto por necrose quanto por apoptose. Sabendo-se que a regeneração do sistema nervoso central é limitada após danos tissulares, é crucial o desenvolvimento de novas abordagens que otimizem o retorno funcional após IME. As opções de tratamento tardio em cães e em gatos não estão disponíveis e os aspectos de segurança e terapeutico do transplante autólogo de células-tronco mesenquimais derivadas de medula óssea (BMMC) não foram ainda descritas anteriormente. O objetivo desta pesquisa é isolar e caracterizar as BMMC em cães e em gatos; selecionar cães e gatos com IME crônica; elaborar uma abordagem terapeutica à IME utilizando BMMC...

Lesion mechanisms and its evolution following spinal cord injury (SCI) involves neuronal death by both necrosis and apoptosis. Since regeneration of the central nervous system is limited after injuries, it is crucial to develop novel approaches that optimize functional recovery aft er SCI. Stem cell-based therapy has been investigated in a number of degenerative and traumatic diseases, including SCI. Late spinal cord injury treatment options in dogs and cats are not available. Neither the safety aspects and therapeutic effects of autologous bone marrow mesenchymal stem cell (BMMC)...

Determining the Best Treatment for Simple Bone Cyst: A Decision Analysis

BACKGROUND: The treatment of simple bone cysts (SBC) in children varies significantly among physicians. This study examined which procedure is better for the treatment of SBC, using a decision analysis based on current published evidence. METHODS: A decision tree focused on five treatment modalities of SBC (observation, steroid injection, autologous bone marrow injection, decompression, and curettage with bone graft) were created. Each treatment modality was further branched, according to the presence and severity of complications. The probabilities of all cases were obtained by literature review. A roll back tool was utilized to determine the most preferred treatment modality. One-way sensitivity analysis was performed to determine the threshold value of the treatment modalities. Two-way sensitivity analysis was utilized to examine the joint impact of changes in probabilities of two parameters. RESULTS: The decision model favored autologous bone marrow injection. The expected value of autologous bone marrow injection was 0.9445, while those of observation, steroid injection, decompression, and curettage and bone graft were 0.9318, 0.9400, 0.9395, and 0.9342, respectively. One-way sensitivity analysis showed that autologous bone marrow injection was better than that of decompression for the expected value when the rate of pathologic fracture, or positive symptoms of SBC after autologous bone marrow injection, was lower than 20.4%. CONCLUSIONS: In our study, autologous bone marrow injection was found to be the best choice of treatment of SBC. However, the results were sensitive to the rate of pathologic fracture after treatment of SBC. Physicians should consider the possibility of pathologic fracture when they determine a treatment method for SBC.

Mid-term Results of Autologous Bone Marrow Transplantation in Osteonecrosis of the Femoral Head / 대한고관절학회지

PURPOSE: This study evaluated mid-term clinical and radiological results of autologous bone marrow transplantation (BMT) for early stage osteonecrosis of the femoral head (ONFH) and analyzed prognostic factors. MATERIALS AND METHODS: From November 2003 to April 2008, 101 hips of 93 patients with early stage ONFH who underwent autologous BMT were followed for at least five years. For clinical results, preoperative and postoperative Harris hip scores (HHS) were evaluated and survival rate was obtained at the point of performing total hip arthroplasty or femoral head collapse progression. Radiologic results were assessed by changes in necrosis size on magnetic resonance imaging performed preoperative and postoperatively. For evaluation of prognostic factors, survival rate was analyzed according to age, gender, etiology, stage, necrosis size, and location. RESULTS: Averaged HHS at latest follow up showed no significant change in comparison with preoperative HHS. Of 101 hips, 35 hips required arthroplasty and six hips were running head collapse. Groups with use of steroid, lateral location of necrosis, large size of necrosis, or large necrotic angles showed lower survival rate. However, age, gender, and stage had no effect. CONCLUSION: In early days, autologous BMT for early ONFH can be considered as a treatment for improvement of clinical features and delay of radiologic progress. However, after some years, there was no effect compared with the natural course of ONFH.

Experimental model of heterotopic ossification in Wistar rats

Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats.

The study of portal vein hemodynamics changes after autologous bone marrow stem cell transplantation / 中国综合临床

Objective To study portal vein hemodynamics changes after autoiogous bone marrow stem cell transplantation in patients with liver cirrhosis. Methods The hemodynamic parameters, including portal vein diameter, average portal blood flow velocity and spleen size, were determined by Colour Doppler Ultrasonography in 50 patients after autologous bone marrow stem cell transplantation and all cases were followed for up to 6 months. Results (1) After autologous marrow stem cell transplantation, the portal vein diameter reduced significantly at different timepoints compared to before the treatment ([1.41 ± 0. 15] cm, [1. 38 ± 0. 11]cm,[1.36±0. 17] cm vs. [1. 53 ±0. 18] cm,t = 1. 987,1.994,1. 976, Ps 0.05). (2) After autologous marrow stem cell transplantation, the average portal blood flow velocity increased significantly at different timepoints compared to before the treatment ([15. 7 ± 3. 6] cm/s, [16. 1 ± 2.4] cm/s, [15. 9 ± 3.0] cm/s vs.[11.4 ± 3. 3] cm/s ,t = 2. 345, 2.460,2. 381, Ps 0.05) . (3) After autologous marrow stem cell transplantation,the spleen size reduced significantly at different timepoints compared to before the treatment ([4.8±0.3]cm,[4.7±0.6]cm,[4.8±0.5]cm vs. [5. 2 ±0. 7]cm,t =2. 289,2. 390,2.425,Ps 0.05) .Conclusion The autologous bone marrow stem cell transplantation can effectively improve the portal vein blood flow,reduce the spleen size,alleviate portal hypertension in patients with liver cirrhosis.

Nursing of percutaneous and transhepatic portal venous autologous bone marrow stem cell transplantation / 中国实用护理杂志

Objective To summarize the nursing experience of treatment of percutaneous and transhepatic portal venous autologous bone marrow stem cell transplantation for chronic hepatic failure.Methods 19 patients who were definitely diagnosed as chronic liver failure received pertinent nursing in different perioperative period of transhepatic portal venous autologous bone marrow stem cell transplantation.Results All of the 19 patients went through perioperative period safely without any adverse reactions or complications.Conclusions In the process of treatment of autologous bone marrow stem cell transplantation for chronic hepatic failure,sufficient preoperative preparation,good communication and close cooperation among doctors,nurses and patients during operation,careful nursing and rehabilitation instruction after operation,are important assurances for autologous bone marrow stem cell transplantation to run smoothly.

Autologous bone marrow transplantation in a dog with lymphoma: a clinical study / Transplante autólogo de medula óssea em um cão com linfoma: ensaio clínico

The objective of this study is to provide the first report of bone marrow transplantation (BMT) in dogs in Brazil. A Rottweiler with cutaneous lymphoma was submitted to a twelve-week Madison-Wisconsin chemotherapy protocol followed by autologous bone marrow transplantation. For this, 10mL kg-1 of bone marrow was collected simultaneously from both iliac crests and cryopreserved in a freezer at -80°C. The conditioning step was performed by administering cyclophosphamide by intravenous route at 400mg m-2. Bone marrow was reinfused after defrosting in a water bath at 37°C. Bone marrow nucleated cell counts before and after freezing, showed a small relative loss of nucleated cells (35.10 and 31.80x10³µL-1 , respectively). Cyclophosphamide induced neutropenia which was reverted by a granulocyte colony-stimulating factor (G-CSF) capable of stimulating hematopoetic reconstitution. On the day 360 after transplant the patient was found to be in complete remission. This study indicates that autologous BMT in a dog with lymphoma submitted to myelosuppressive chemotherapy was potentially safe and effective.

Este estudo teve como objetivo descrever o primeiro relato de transplante de medula óssea (TMO) em cães no Brasil. Para tanto, um rottweiller com linfoma cutâneo foi submetido ao protocolo quimioterápico de Madison-Wisconsin pelo período de 12 semanas, seguido pelo transplante autólogo de medula óssea. Para tanto, 10mL kg-1 de medula óssea foram coletados de ambas as cristas ilíacas do paciente, simultaneamente; sendo o volume final criopreservado em freezer a -80°C. A etapa de condicionamento foi realizada com a administração da ciclofosfamida, por via intravenosa, na dose de 400mg m-2. A reinfusão da medula óssea foi realizada após o descongelamento da bolsa em banho-maria a 37°C. As contagens de células nucleadas de alíquotas obtidas da bolsa de medula óssea antes do congelamento e após o descongelamento demonstram pequena perda relativa de células nucleadas (35,10 e 31,80 x10³µL-1, respectivamente). A neutropenia decorrente da ciclofosfamida foi revertida com a administração de um fator estimulador de colônia de granulócitos (G-CSF), que foi capaz de acelerar a reconstituição hematopoética. O paciente encontra-se no dia + 360 pós-transplante em remissão completa da doença. Este trabalho indicou que o TMO autólogo em um cão com linfoma, submetido à quimioterapia mielossupressora, foi potencialmente seguro e efetivo.

Efficacy and Safety of Autologous Bone Marrow-derived Mesenchymal Stem Cell Treatment in Patients With Amyotrophic Lateral Sclerosis

BACKGROUND: This study was performed to investigate the efficacy and safety of intrathecal autologous bone marrowderived mesenchymal stem cells (MSCs) treatment for patients with ALS. METHODS: After a lead-in period for 3 months, 22 patients were treated with MSCs twice at an interval of 1 month. After initial MSCs injection, all patients were followed up for 3 months and their disease course, clinical characteristics were assessed. Disease status of patients were analyzed with ALS functional rating scale-revised (ALSFRS-R) for primary outcome measure, and additional clinical findings after treatment were all collected for secondary outcome measure and safety. Age and disease-duration matched patients with ALS were selected as a control group. RESULTS: During the follow-up period, MSCs treatment yielded a significant lesser change of ALSFRS-R score, compared to control group (1.54 vs 3.56, p<0.01). Moreover, the slop of decline of ALSFRS-R was significantly lower during the follow-up period, compared to the lead-in period in MSCs treatment group (2.68 vs 1.54, p=0.04), whereas the slopes during the two periods were not different in the control group (3.15 vs 3.56, p=0.37). MSCs treatment was well tolerated except for occurrences of transient headache, low back pain, and myalgia. CONCLUSIONS: Our results show that intrathecal MSCs injection can slow disease progression and might be used as a disease modifying modality as an alternative treatment choice in patients with ALS.

Clinical study of autologous transplantation of bone-marrow mononuclear cells for treating patients with diabetic lower limb ischemia / 中国医师进修杂志

Objective To investigate the efficiency of autologous transplantation of bone-marrow mononuclear cells for treatment of patients with diabetic lower limb ischemia. Methods Twenty patients of type 2 diabetes (22 legs) with diabetic lower limb ischemia were treated by autologous transplantation of bone-marrow mononuclear cells. Results All ischemic legs were preserved except three feet, which were amputated due to the previously existed foot gangrene in one and unsolved pain in two. The pain-alleviated rate was 85.0%. The amputation rate was 13.6%. The skin turned warm in all legs(100.0%). TcPO2 of the ischemic legs was elevated in 17 patients with 19 legs. Angiography showed a noticeable increase of visible collateral vessels in 7 patients with 8 limbs who had angiographic follow-up. Conclusion Autologous transplantation of bone-marrow mononuclear cells could be a simple, safe, and effective method to treat patients with diabetic lower limb ischemia.

Autologous bone-marrow mononuclear cells transplantation in experimental acute myocardial infarction / 中国康复理论与实践

@#ObjectiveTo investigate the survival and differentiation of autologous bone-marrow mononuclear cell (ABM-MNCs) after transplanted to infarcted area and border area, and the effect of ABM-MNC on the cardiac function.Methods40 male big-ear Japanese rabbits were divided randomly into the transplanted group and control group with 20 animals in each group. Acute myocardial infarction model was made by ligating left anterior descending artery. 7 days later, Brdu labeled ABM-MNCs were injected into myocardium in the transplanted group, while the control rabbits were injected with saline. Six weeks later, tests of histology and immunohistochemistry were performed.ResultsViable cells labeled with Brdu can be identified in the infarcted area, and myocytes and endothelial cells labeled with Brdu can also be found in the border area, these cells demonstrated myogenic differentiation with the expression of α-actin by immunostaining. While, no cells labeled with Brdu were found in the control group. Moreover, the vessel density of the transplanted group in the borders of the infarction was higher than the control group (P<0.05), but there was no difference in infarcted area between two groups (P>0.05).At the 6 weeks after experiment, the cardiac function was improved in both groups, but there was a significant difference between two groups (P<0.05).ConclusionABM-MNCs injected into the infarcted myocardium can survive in both the infarcted and border areas, and differentiate into endothelial cells and other cells which are able to obtain the characters of myocytes, and increase the vessel density in border area, improve the cardiac function.

Autologous Bone Marrow Cell Transplantation Combined with Off-Pump Coronary Artery Bypass Grafting in Human Ischemic Myocardium

Recently, autologous bone marrow cell transplantation (CTx) for angiogenesis and myogenesis in ischemic myocardium has been extensively investigated to improve heart function. This study was designed to evaluate the effects of CTx with off-pump coronary artery bypass grafting (OPCAB) in patients who were not feasible for complete revascularization. Seven male patients underwent CTx combined with OPCAB in 5, CTx only in 1, and mitral valve repair in 1 patient simultaneously. Bone marrow was aspirated from iliac bone. Mean 1.5 x109 mononuclear cells including mean 7.3 x106 CD34+ cells and 2.4 x106 AC133+ cells were obtained and concentrated with 10cc. These cells were transplanted into non-graftable ischemic myocardium. Heart function was evaluated in all patients using MIBI scan, echocardiogram and heart magnetic resonance imaging (MRI) preoperatively. The effect of CTx was evaluated using MIBI scan, echocardiogram, and MRI postoperatively. An average of 2 grafts were bypassed. Other territories were transplanted with isolated mononuclear cell. All patients had an uncomplicated postoperative course. After 2 to 7 months follow-up, there was improvement in symptom, ejection fraction (from 43% to 47%) on echocardiogram and myocardial perfusion on MIBI scan and MRI in all patients. These preliminary data showed improvement of heart function and myocardial perfusion and also showed the feasibility and safety of combined therapy with OPCAB and CTx in ischemic myocardium. However, the effectiveness of CTx alone cannot be readily assessed. Further randomized, controlled studies are required to evaluate the effectiveness of CTx alone.

Functional expression and temporality of MDR1 gene in bone marrow of rabbits after autologous transplantation with the gene modification to mononuclear cells / 第三军医大学学报

Objective To explore the functional expression and temporality of MDR1 gene in bone marrow of rabbits after autologous bone marrow transplantation with MDR1 transferred bone marrow mononuclear cells. Methods The supernatant of the amphotropic virus producer cell line PA317-HaMDR1/A was collected and concentrated to cocultivate with the bone marrow mononuclear cells of the rabbits. After large dose of chemotherapy with cyclophosphamide,the transferred cells were autotransplanted into the bone marrow. The integration,transfection rate and physiological function of MDR1 gene were tested by PCR,SP immunohistochemical method and daunorubicin (DNR) extrusion test respectively. Results After autologous bone marrow transplantation had been executed for 1-4 months,the integration of MDR1 gene in genome of bone marrow mononuclear cells was detected by PCR,and the expression rates of P-gp in cells tested by SP immunohistochemical method were 9.5%,8.5%,6.0% and 3.5% respectively. The physiological function of MDR1 gene in bone marrow cells was proved by DNR extrusion test. Conclusion After the autotransplantation with bone marrow mononuclear cells transferred by MDR1 gene,the MDR1 gene can implant into the bone marrow of rabbits and has expressed functionally for 4 months,which has provided a basis for further research on chemoprotection experiment of the MDR1 gene transferred into the bone marrow cells.

Clinical study of autologous bone marrow transplantation in the treatment of 35 patients with acute leukemia / 中国医师杂志

Objective To evaluate the clinical effects of autologous bone marrow transplantation(ABMT) in the treatment of patients with acute leukemia.Methods A retrospective study was accomplished on the ABMT in the treatment of 35 patients with acute leukemia from Oct 1999 to Oct 2004.The median age of the patients was 32.5(9～55) years.Of the 35 patients,26 cases were acute non-lymphocytic leukemia(ANLL) and 9 cases were acute lymphoblastic leukemia(ALL).The patients were pretreated with melphalan(140～180mg/m~2),cyclophosphamide(120mg/kg) and arabinosylcytosin(3g/m~2).Results All patients engrafted successfully.The median follow-up duration was 756(186～1950) days.The 3-year probabilities of disease-free-survival(DFS) for ANLL and ALL were(65.4%?8.9)% and(33.3?13.6)% respectively,and the probabilities of relapse were(30.6?9.2)% and(60.7?25.5)%,respectively.Conclusion To decrease relapse and increase DFS,patients with acute leukemia who have no chance for allogene haemopoietic stem cell transplantation are recommended for ABMT.