Autologous Mesenchymal Stem Cell Transplantation Research Articles

Clinical Efficacy of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Patients with Refractory Cirrhotic Ascites

Objective: To analyze the efficacy of autologous bone marrow mesenchymal stem cell (BMSC) transplantation for the treatment of cirrhotic ascites (refractory). Methods: 64 patients with cirrhosis ascites (refractory) who were admitted to the hospital between May 2022 and April 2024 were selected and divided equally by random number table, the observation group was treated with BMSC autologous transplantation, and the reference group was treated with conventional medication, and the total effective rate, therapeutic indexes, liver and renal function indexes, and the change of urine volume were compared. Results: The total effective rate of the observation group was higher than that of the reference group (P < 0.05). Before treatment, there was no difference between the two groups in terms of therapeutic indexes such as depth of ascites, liver and kidney function indexes and 24-hour urine volume (P > 0.05). After treatment, the observation group’s ascites depth and other indicators were better than that of the reference group, liver and kidney function indicators were better than that of the reference group, and 24h urine volume was more than that of the reference group (P < 0.05). Conclusion: BMSC autotransplantation can improve the clinical efficacy of patients with cirrhosis ascites (refractory), accelerate the absorption of ascites, reduce the values of body mass and abdominal circumference, and protect the liver and kidney functions and increase the amount of urination.

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial

BackgroundInflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients.MethodsThis study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines.ResultsDuring the study’s follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients.ConclusionAD-MSCs represent a potential intervention to prevent age-related inflammation in patients.Trial registrationClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020

Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review.

Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.

Efficacy of Neonatal Porcine Bone Marrow-Derived Mesenchymal Stem Cell Xenotransplantation for the Therapy of Hind Limb Lymphedema in Mice.

Lymphedema is an intractable disease with few effective therapeutic options. Autologous mesenchymal stem cell (MSC) transplantation is a promising therapy for this disease. However, its use is limited by the cost and time for preparation. Recently, xenotransplantation of porcine MSCs has emerged as an alternative to autologous MSC transplantation. In this study, we aimed to clarify the usefulness of neonatal porcine bone marrow-derived MSC (NpBM-MSC) xenotransplantation for the treatment of lymphedema. One million NpBM-MSCs were xenotransplanted into the hind limbs of mice with severe lymphedema (MSC transplantation group). The therapeutic effects were assessed by measuring the femoral circumference, the volume of the hind limb, the number and diameter of lymphatic vessels in the hind limb, and lymphatic flow using a near-infrared fluorescence (NIRF) imaging system. We compared the effects using mice with lymphedema that did not undergo NpBM-MSC transplantation (negative control group). The condition of the transplanted NpBM-MSCs was also evaluated histologically. The femoral circumference and volume of the hind limb had been normalized by postoperative day (POD) 14 in the MSC transplantation group, but not in the negative control group (P = 0.041). NIRF imaging revealed that lymphatic flow had recovered in the MSC transplantation group by POD 14, as shown by an increase in luminance in the hind limb. Histological assessment also showed that the xenotransplantation of NpBM-MSC increased the proliferation of lymphatic vessels, but they had been rejected by POD 14. The xenotransplantation of NpBM-MSCs is an effective treatment for lymphedema, and this is mediated through the promotion of lymphangiogenesis.

The closest results of the autologous mesenchymal stem cell transplantation in patient with type 1 diabetes mellitus in the honeymoon phase

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Autologous Synovial Mesenchymal Stem Cell Transplantation Suppresses Inflammation Caused by Synovial Harvesting and Promotes Healing in a Micro Minipig Repaired Meniscus Model

Allogeneic synovial mesenchymal stem cells (MSCs) effectively promote meniscus healing in micro minipigs. We investigated the effect of autologous synovial MSC transplantation on meniscus healing in a micro minipig model of meniscus repair showing synovitis after synovial harvesting. Synovium was harvested from the left knee of the micro minipigs after arthrotomy and used to prepare synovial MSCs. The left medial meniscus in the avascular region was injured, repaired, and transplanted with synovial MSCs. First, synovitis was compared after 6 weeks in knees with and without synovial harvesting. Second, the repaired meniscus was compared for the autologous MSC group and the control group (in which synovium was harvested but MSCs were not transplanted) 4 weeks after transplantation. Synovitis was more severe in knees subjected to synovium harvesting than in knees not subjected to harvesting. Menisci treated with autologous MSCs showed no red granulation at the tear of the meniscus, but menisci not treated with MSCS showed red granulation. Macroscopic scores, inflammatory cell infiltration scores, and matrix scores assessed by toluidine blue staining were all significantly better in the autologous MSC group than in the control group without MSCs (n=6). Autologous synovial MSC transplantation suppressed the inflammation caused by synovial harvesting in micro minipigs and promoted healing of the repaired meniscus.

Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies.

In cell transplantation therapy, mesenchymal stem cells(MSCs)are ideal seed cells due to their easy acquisition and cultivation, strong regenerative capacity, multi-directional differentiation abilities, and immunomodulatory effects. Autologous MSCs are better applicable compared with allogeneic MSCs in clinical practice. The elderly are the main population for cell transplantation therapy, but as donor aging, MSCs in the tissue show aging-related changes. When the number of generations of in vitro expansion is increased, MSCs will also exhibit replicative senescence. The quantity and quality of MSCs decline during aging, which limits the efficacy of autologous MSCs transplantation therapy. In this review, we examine the changes in MSC senescence as a result of aging, discuss the progress of research on mechanisms and signalling pathways of MSC senescence, and discuss possible rejuvenation strategies of aged MSCs to combat senescence and enhance the health and therapeutic potential of MSCs.

Autologous Adipose-Derived Mesenchymal Stem Cell Transplantation for Management of Chronic Kidney Disease Patients: A Clinical Trial in Human

The current clinical trial presents a review of CKD-patients enrolled for Autologous Adipose-Derived Mesenchymal Stem Cells (adMSCs) transplantation at Bangladesh Laser & Cell Surgery (BLCS) Institute & Hospital. Between April 2019 to June 2021, 52 CKD-patients were enrolled in this phase 1 & 2 trial receiving intravenous autologous adMSCs transplantation. Twenty-three CKD-patients who had received MSCs transplantation and had also followed-up with di-ethylene tri-amine Penta-acetic acid (DTPA) -based glomerular filtration rate (GFR) assessment, were considered for analysis. The mean (SD) DTPA-based GFR was significantly improved after adMSCs transplantation among study participants than the baseline mean (SD) DTPA-based GFR (19.79 [12.4] vs 15.07 [11.4], p=0.003). The DTPA-based GFR improved in stage-5 CKD patients with and without dialysis after MSCs transplantation, but a significant mean difference was observed only in CKD patients on dialysis (7.1 [6.9] vs 14.2 [12.6], p=0.011). Hence, pre-dialysis patients DTPA-GFR both at baseline and endline was higher than patients those on dialysis. The obtained results revealed that renal function improves in CKD patients through MSCs transplantation. No significant side effects or complication pertaining specifically to stem cell transplantation was observed during the study period.

Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial

BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients.MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation.ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices.ConclusionsTaken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes.Trial registration: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308).

Role of Inflammatory Niche and Adult Cardiomyocyte Coculture on Differentiation, Matrix Synthesis, and Secretome Release by Human Bone Marrow Mesenchymal Stem Cells.

Myocardial infarction (MI) causes cardiomyocyte death, provokes innate immune response, and initiates tissue remodeling. The intrinsic healing process is insufficient to replace the lost cells, or regenerate and restore the functional features of the native myocardium. Autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation is being explored to offer therapeutic potential after MI. Here, we cultured human BM-MSC spheroids in three-dimensional collagenous gels for 28days under exposure to tumor necrosis factor-alpha (+ TNFα), and coculture with adult human cardiomyocytes, or with conditioned media (CM) pooled from TNFα-stimulated adult cardiomyocytes. MSC differentiation marker (CD90, GATA4, cTnI, cTnT, Cx43, MHC, α-actin) expression, matrix protein (elastin, hyaluonic acid, sulfated glycosaminoglycans, laminin, fibrillin, nitric oxide synthase) synthesis, and secretome (cytokines, chemokines, growth factors) release at days 12 and 28 were assessed. MSC density decreased with duration in all culture conditions, except in controls. GATA4 expression was higher in cocultures but lower in + TNFα cultures. Synthesis and deposition of various extracellular matrix proteins and lysyl oxidase within MSC cultures, as well as secretome composition, were strongly dependent on the culture condition and duration. Results suggest that TNFα-induced inflammation suppresses BM-MSC survival and differentiation into mature cardiomyocytes by day 28, while promoting matrix protein synthesis and cytokine release conducive to MI remodeling. These findings could have implications in developing tissue engienering and cell transplantation strategies targeting MI, as well as to develop therapuetics to target inflammation-induced matrix remodeling post-MI.

MESENCHYMAL STEM CELL-BASED THERAPY FOR CHRONIC KIDNEY FAILURE RELATING LUPUS ERYTHEMATOSUS - A CASE REPORT

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which is characterized by systemic multiple-organ involvement, relapses with large amount of autoantibodies. Their pathophysiology is multifaceted, involves complex hormonal-immunological-cellular interactions, and leads to damage in multiple cell types, which is often resistant to conventional therapy. Thus, novel strategies are needed to repair the renal parenchyma and preserve kidney function. Mesenchymal stem cells (MSC) confer renal protection through paracrine/endocrine effects, and to some degree possibly by direct engraftment. The patient was diagnosed with chronic kidney disease by standard methods for more than fifteen years. The patient agreed to the treatment of autologous adipose mesenchymal stem cell transplantation. The adipose mesenchymal stem cells were harvested by surgery, isolated with our enzyme protocol. The patient received one injection with 2,6x106 cells/kg for a total of 43kg of body weight. The patient with SLE do not receive prompt treatment, he get irreversible organ damage. After seven months, the preexisting renal insufficiency gradually ameliorated, including the decrease of creatinine and blood urea as well as the increase of estimated glomerular filtration rate. Lupus symptoms also reduced, followed by the improvement of body movement and medication reduction.There was insufficient evidence of the clinical setting to show the efficiency of mesenchymal stem cells on the lupus nephritis relating to chronic kidney disease. This clinical trial highlights the feasibility and safety of mesenchymal stem cell treatments in renal failure-associated- autoimmune diseases.

Abstract MP243: Detection Of Mesenchymal Stem Cells In Mobilized Autologous Peripheral Blood Transplantation From Patients With Ischemic Heart Disease

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.

Autologous Placenta-derived Mesenchymal Stem Cell Transplantation for Labored Pregnant Patients With COVID-19

Coronavirus Disease 2019 (COVID-19) is one of the most critical health issues in the world. According to the findings, systemic proinflammatory cytokine release is associated with the pathogenesis of cytokine storm, contributing to morbidities and even mortality in patients diagnosed with COVID-19. Among pregnant patients diagnosed with COVID-19, preterm labor is one of the most crucial side effects, with a prevalence of up to 63.8% in some studies. As well as cytokine storm, proinflammatory cytokines are involved in preterm labor. Mesenchymal Stem Cells (MSCs) transplantation has been used in different trials to suppress inflammation in many inflammatory diseases. MSCs have also been successfully applied to treat patients diagnosed with COVID-19, considering the cytokine storm in these patients. So, it is possible to use the transplantation of MSCs derived from the maternal side of the placenta as an autologous product to suppress cytokine storm in critically ill patients diagnosed with COVID-19. The autologous transplantation of MSCs helps to suppress cytokine storm and systemic inflammation. Inhibition of systemic cytokine release could prevent poor outcomes, especially mortality and morbidities in the mentioned patients.

Can Autologous Adipose-Derived Mesenchymal Stem Cell Transplantation Improve Sexual Function in People with Sexual Functional Deficiency?

Sexual functional deficiency occurs at some point in life and becomes a problematic issue in middle-aged adulthood. Regenerative medicine, especially mesenchymal stem cell (MSC) transplantation, has developed extensively, with preclinical and clinical trials emphasizing the benefits of stem cell therapy for restoration of sexual deficiency. This study was designed to develop a new therapeutic stem cell treatment for people with sexual functional deficiency. Thirty-one patients, including 15 males and 16 females with a medical history of reduced sexual activity, met the inclusion criteria and were enrolled in the study, phase I/IIa clinical trial with a 12-month follow-up. Adipose tissue-derived mesenchymal stem/stromal cells (ADSC) were isolated by type I collagenase digestion and cultured at the Stem Cell Core Facility under ISO 14644-1. Each participant received 1 million cells/kg of body weight via the intravenous route. Safety was evaluated by assessing the occurrence of adverse events or severe adverse events. Efficacy was assessed in males by monitoring testosterone levels and administering the International Index of Erectile Function (IIEF) questionnaire and in females by monitoring anti-Mullerian hormone (AMH), estradiol (E2), and follicle-stimulatinghormone (FSH) levels and administering the Female Sexual Functioning Index (FSFI) questionnaire at baseline and 3-, 6-, and 12-months post-transplantation. There was no occurrence of severe adverse events after ADSC administration in our study. Post-transplantation sexual satisfaction was observed in all patients enrolled in this study. Testosterone levels in males increased soon after transplantation and were maintained at high levels for up to 6 months before decreasing again at the 12-month follow-up. No significant changes in AMH,FSH or E2 levels were recorded in female patients. Autologous ADSC infusion is a potential therapeutic option for patients with reduced sexual activity, especially for male patients. ClinicalTrials.gov. NCT03346967, Registered November 20, 2017.

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, multicenter, randomized controlled trial

ObjectiveOur aim was to evaluate the efficacy and safety of intracoronary autologous bone marrow mesenchymal stem cell (BM-MSC) transplantation in patients with ST-segment elevation myocardial infarction (STEMI).MethodsIn this randomized, single-blind, controlled trial, patients with STEMI (aged 39–76 years) were enrolled at 6 centers in Beijing (The People’s Liberation Army Navy General Hospital, Beijing Armed Police General Hospital, Chinese People’s Liberation Army General Hospital, Beijing Huaxin Hospital, Beijing Tongren Hospital, Beijing Chaoyang Hospital West Hospital). All patients underwent optimum medical treatment and percutaneous coronary intervention and were randomly assigned in a 1:1 ratio to BM-MSC group or control group. The primary endpoint was the change of myocardial viability at the 6th month’s follow-up and left ventricular (LV) function at the 12th month’s follow-up. The secondary endpoints were the incidence of cardiovascular event, total mortality, and adverse event during the 12 months’ follow-up. The myocardial viability assessed by single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was used to assess LV function. All patients underwent dynamic ECG and laboratory evaluations. This trial is registered with ClinicalTrails.gov, number NCT04421274.ResultsBetween March 2008 and July 2010, 43 patients who had underwent optimum medical treatment and successful percutaneous coronary intervention were randomly assigned to BM-MSC group (n = 21) or control group (n = 22) and followed-up for 12 months. At the 6th month’s follow-up, there was no significant improvement in myocardial activity in the BM-MSC group before and after transplantation. Meanwhile, there was no statistically significant difference between the two groups in the change of myocardial perfusion defect index (p = 0.37) and myocardial metabolic defect index (p = 0.90). The LVEF increased from baseline to 12 months in the BM-MSC group and control group (mean baseline-adjusted BM-MSC treatment differences in LVEF 4.8% (SD 9.0) and mean baseline-adjusted control group treatment differences in LVEF 5.8% (SD 6.04)). However, there was no statistically significant difference between the two groups in the change of the LVEF (p = 0.23). We noticed that during the 12 months’ follow-up, except for one death and one coronary microvascular embolism in the BM-MSC group, no other events occurred and alanine transaminase (ALT) and C-reactive protein (CRP) in BM-MSC group were significantly lower than that in the control group.ConclusionsThe present study may have many methodological limitations, and within those limitations, we did not identify that intracoronary transfer of autologous BM-MSCs could largely promote the recovery of LV function and myocardial viability after acute myocardial infarction.

Effectiveness of Autologous Schwann Cell and Bone Marrow-Derived Mesenchymal Stem Cell Transplantation for Individuals With Spinal Cord Injury in Promoting Sensory Recovery

Background: In recent decades, improvement in sensory and motor function after spinal cord injury(SCI) is a major treatment goal. Stem cell therapy has become a promising treatment strategy in theregeneration of central nervous system injuries.Methods: We assessed the effectiveness of autologous Schwann cell (SC) and bone marrow-derivedmesenchymal stem cell (MSC) for individuals with SCI in promoting sensory recovery. Five patientswith a mean ± SD age of 38.80 ± 5.84 years were enrolled in the study. The follow-up course was12 months.Results: We found sensory changes in two patients assessed by the American Spinal InjuryAssociation’s (ASIA’s) impairment scale. Systemic complications were not observed during thecourse of the study.Conclusion: There were no adverse finding after cell transplantation. Also we observed improvementin sensory score in two patients. It seems that the use of this combination of cell therapy may beeffective; but large group studies with control group are required to clarify the effect of either cells.

Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis.

In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.

The long-term outcomes of cell c ardiomyoplast y in patients with refractory angina

he long-term outcomes of cellular cardiomyoplasty in patients with ischemic cardiac dysfunction were studied. The results of treatment of 45 patients aged 46–70 years, mean age is (56.8±19.7) years, who were hospitalized in the Emergency and Reconstmctive Cardiac Surgery Department of the "V.K. Gusak Institute of Emergency and Reconstmctive Surgery of NAMS of Ukraine" from 2007 to 2013 were analyzed. It was established that the transplantation of autologous mesenchymal bone marrow stem cells using the navigation system is a safe and effective procedure, that helps to increase the survival rates up to 35 (18–61) months compared to 12 (0.72-50.0) months in the group of pharmacological therapy (p value = 0.033). Also the reduction of mortality 36 months after the stem cells injection to 13.3% compared to 46.7% in the group of pharmacological treatment in the same terms was observed. To achieve the maximum effect of treatment, it is reasonable to repeat the procedure of autologous mesenchymal bone marrow stem cells transplantation 1 year later after the first procedure. Endomyocardial implantation of autologous mesenchymal bone marrow stem cells improves basic dimensions of life quality: physical functioning, pain intensity, usual activity and social functioning regardless of the initial severity of ischemic dysfunction. Keywords: stem cells, cardiomyoplasty, heart failure, refractory angina.

Autologous Bone Marrow Mesenchymal Cell Transplantation in the Treatment of Freiberg's Disease: Case Report

Background: Osteonecrosis of the metatarsal head, classically known as Freiberg's disease, presents as aseptic necrosis of the epiphysis of undefined etiology, although it may be associated with trauma, prolonged corticotherapy or systemic diseases such as sickle cell disease. There are several techniques described for the treatment of osteonecrosis secondary to sickle cell disease. Methods: Case report and the surgical description of the use of autologous bone marrow mesenchymal stem cell transplantation for the treatment of osteonecrosis of the 2nd metatarsal head. Results: Nuclear magnetic resonance imaging performed after one year of follow-up showed a regression of the findings found in the preoperative evaluation. Conclusion: This is the first time that the technique of autologous bone marrow mesenchymal stem cell implantation has been employed for the treatment of osteonecrosis of the metatarsal head. The case reported shows that the technique is safe and brings good results after conservative treatment failure.

Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells

Recent progress in the field of mesenchymal stem cell (MSC) biology has enabled their clinical application. In the autologous cell transplantation therapy, the source of MSCs are quite important to reduce patients’ physical burden. In this study, we isolated MSCs from the synovial fluid (SF) and synovial membrane (Syn) of the same patients and compared the biological characteristics of them. In vitro and in vivo experiments indicated the non-inferior chondrocytic differentiation and articular cartilage regeneration potential of SF-MSCs compared to that of Syn-MSCs; however, SF-MSCs showed less proliferative potential than Syn-MSCs in vitro. Flow cytometry-based multiplex surface antigen expression analyses indicated that SF-MSCs exhibit fewer cells positive for CD140, which is a functional growth factor receptor for MSCs. Nevertheless, we obtained enough SF-MSCs for transplantation within several passages. Since arthrocentesis is routinely performed during outpatient care in the consultation room and is less invasive than synovial biopsy, MSC derived from synovial fluid could be considered an attractive cell source for cartilage regenerative therapy as a substitute for Syn-MSC. Developing these cells for clinical application may greatly benefit patients undergoing autologous MSC transplantation therapy.