Marrow-derived Stem Cell Therapy Research Articles

Bone marrow transplantation and bone marrow-derived mesenchymal stem cell therapy in epidermolysis bullosa: A systematic review.

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.

Bone Marrow-derived Mesenchymal Stem Cell Therapy in Retinitis Pigmentosa.

To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa. Stem cell treatment in retinitis pigmentosa provides improvement in visual acuity and visual field. Forty-seven eyes of 27 patients diagnosed with retinitis pigmentosa were included in our study. Allogeneic bone marrow-derived mesenchymal stem cells were administered by deep subtenon injection. Complete routine ophthalmological examinations, optical coherence tomography (Zeiss, Cirrus HD-OCT) measurements, and visual field (Humphrey perimetry, 30-2) tests were performed on all patients before the treatment and on the 1st, 3rd, and 6th month after treatment. The best corrected visual acuities of the patients were determined by the Snellen chart and converted to logMAR. Visual evoked potential (VEP) and electroretinogram (ERG) examinations of the patients before the treatment and on the 6th month after the treatment were performed (Metrovision) data were compared. Visual acuities were 0.74 ± 0.49 logMAR before treatment and 0.61 ± 0.46 logMAR after treatment. Visual acuity had a statistically significant increase (p < 0.001). The visual field deviation was found to be -27.16 ± 5.77 dB before treatment and -26.59 ± 5.96 dB after treatment (p = 0.005). The ganglion cell layer was 46.26 ± 12.87 μm before treatment and 52.47 ± 12.26 μm after treatment (p = 0.003). There was a significant improvement in Pattern VEP 120º P100 amplitude compared to that before the treatment (4.43 ± 2.42 μV) and that after the treatment (5.09 ± 2.86 μV) (p = 0.013). ERG latency measurements were 18.33 ± 15.39 μV before treatment and 20.87 ± 18.64 μV after treatment for scotopic 0.01 (p = 0.02). ERG latency measurements for scotopic 3.0 were 20.75 ± 26.31 μV before treatment and 23.10 ± 28.60 μV after treatment (p = 0.014). Retinitis pigmentosa is a progressive, inherited disease that can result in severe vision loss. In retinitis pigmentosa, the application of bone marrow-derived mesenchymal stem cells by deep subtenon injection has positive effects on visual function. No systemic or ophthalmic side effects were detected in the patients during the 6-month follow-up period.

Intra-amniotic mesenchymal stem cell therapy improves the amniotic fluid microenvironment in rat spina bifida aperta fetuses.

Spina bifida aperta (SBA) is one of the most common neural tube defects. Neural injury in SBA occurs in two stages involving failed neural tube closure and progressive degeneration through contact with the amniotic fluid. We previously suggested that intra-amniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for fetal rat SBA could achieve beneficial functional recovery through lesion-specific differentiation. The aim of this study is to examine whether the amniotic fluid microenvironment can be improved by intra-amniotic BMSC transplantation. The intra-amniotic BMSC injection was performed using in vivo rat fetal SBA models. The various cytokine expressions in rat amniotic fluid were screened by protein microassays. Intervention experiments were used to study the function of differentially expressed cytokines. A total of 32 cytokines showed significant upregulated expression in the BMSC-injected amniotic fluid. We focused on Activin A, NGF, BDNF, CNTF, and CXCR4. Intervention experiments showed that the upregulated Activin A, NGF, BDNF, and CNTF could inhibit apoptosis and promote synaptic development in fetal spinal cords. Inhibiting the activity of these factors weakened the anti-apoptotic and pro-differentiation effects of transplanted BMSCs. Inhibition of CXCR4 activity reduced the engraftment rate of BMSCs in SBA fetuses. BMSC transplantation can improve the amniotic fluid environment, and this is beneficial for SBA repair.

Stem cell therapy for type1 diabetes with transplantation of stem cells into the Omental pouch, peritoneum, and blood, experimental study

IntroductionType 1 diabetes is a dreadful autoimmune disease of childhood with incidence of 0.26/1000 children in India. To develop a new, cheap, and effective treatment for this disease, we invented an autologous Stem cell therapy for type 1 diabetes in which stem cells are transplanted into the Omental pouch, peritoneum, and blood. The Omental pouch stem cell operation in the therapy is reported for the first time in the medical literature. Materials and methodsLast 5 years I treated 21 patients of Type 1 diabetes with autologous stem cell therapy and in the same period, a group of 26 patients of Type 1 diabetes with conventional treatment of Insulin injections was put as a control group. Blood sugar fasting and post prandial, Anti Gad antibody titer, Glycosylated Hb and C peptide levels and weight of patient and total Insulin requirement in 24 h were the variables to be measured before the therapy and after the therapy. Stem cells were harvested from patients own bone marrow and separated by density gradient method. An infusion of 20 mg/kg methylprednisolone in 100 ML normal saline given intravenously over 1 h prior to the therapy. The total average numbers of cells harvested were 7.86 × 107. One third quantity of isolated stem cells were put into the Omental pouch through no. 7 IFT, another one third into peritoneal cavity through no. 10 IFT and remaining third is given IV in 100 ml normal saline. ResultsThe minimum follow up was 6 months and maximum of 4 years. In the therapy group, the average weight gain after one year of therapy, daily requirement of Insulin and its drop after therapy, drop in HbA1c levels, drop in fasting and post prandial blood sugar, rise of C peptide levels and drop in Anti-GAD antibody titer were measured and was found to be statistically highly significant. The same parameters were measured in control group and was not statistically significant. There were a few side effects noted after stem cell therapy such as mild skin rash, nausea, and pain in abdomen. DiscussionIn autologous bone marrow derived stem cell therapy, cells are transplanted into the Omental pouch, peritoneum, and blood. Cells transplanted in the Omental pouch get vascularized like a split skin graft. Omental surface has far less cellular immunity than blood, hence, if some of these cells get converted into Islets like cells producing Insulin, then they are less vulnerable to damage by the immune system. It means that the Omental pouch may act as a new biological pancreas producing Insulin. Stem cells injected intravenously reach the pancreases and may get differentiate into Islet like cells due to specific growth factors released by pancreas. Stem cells can reverse autoimmunity by their immunomodulatory function. Stem cells transplanted in peritoneum grow longer due to large surface area and little cellular immunity and secrete growth factors and cytokines for a long time which can rejuvenate existing Islets of Langerhans. The therapy group had substantially good results compared to the control group and the difference was statistically highly significant. ConclusionsAutologous stem cell therapy was safe, and effective for the long term for the treatment of Type 1 diabetes. We need a greater number of cases and a longer follow up to make it better. The therapy creates a lot of hope for Type 1 diabetes patients as it can be easily repeated any number of times.

Treatment of Pulmonary Sarcoidosis Using Allogenic Bone Marrow-Derived Mesenchymal Stem Cell Therapy is Safe: A Case Report

Mesenchymal stem cells have a proven potent immunomodulatory effect both in vitro and in vivo. We report a case of a 67-year-old male patient, first diagnosed with sarcoidosis in 2005, that responded well clinically and biologically to ImmunoARTTM (developed by Educell Ltd.) allogenic, HLA-incompatible, and non-related bone marrow-derived MSCs in a dose of 106/kg. The patient presented to St. Catherine Specialty Hospital in 2021 with an exacerbation of respiratory symptoms. After a clinical and radiological examination with laboratory workup, radiological findings were consistent with pulmonary sarcoidosis, while laboratory work revealed increased leucocytes at 14.2 g/L, CRP at 51.2 mg/L, and lymphocytes at 4.25 g/L. The patient was then administered intravenous application of MSCs on three occasions in the out-patient clinic. MSC doses were prepared from a young, healthy donor who agreed to donate bone marrow for allogeneic treatment and who was negative for viral markers (HBs Ag, HBc Ab, HCV Ab, HIV 1-2 Ab, TPHA, HBV NAT, HCV NAT, HIV NAT) according to EU legislation. Cells were prepared in a controlled and verified laboratory for “Hospital exemption” cell preparation in the cleanroom facility in safety cabinet class A and expressed CD105, CD 73, and CD 90 but lacked the expression of CD45 and CD34. Before the treatment, standard print and detailed verbal information were provided to patients undergoing treatment. Immediately after the informed consent form (ICF) was signed by the patient. Throughout MSC therapy, the patient showed an improvement clinically and biologically with a decrease in inflammatory parameters. Laboratory values were assessed on days 2, 5, and 7. On day 7, leucocytes were 11.2 g/L, CRP 5.1 mg/L, and lymphocytes 4.0 g/L. In the follow-up period, the patient felt subjectively better, without any side effects of the MSC therapy. Unfortunately, the patient dropped out from follow-up, therefore, the prolonged effects of this therapy were not able to be assessed. Therefore, systemic MSC therapy presents an opportunity to treat sarcoidosis that needs to be further researched.

Treatment of Pulmonary Sarcoidosis Using Allogenic Bone Marrow-Derived Mesenchymal Stem Cell Therapy is Safe: A Case Report

Treatment of Pulmonary Sarcoidosis Using Allogenic Bone Marrow-Derived Mesenchymal Stem Cell Therapy is Safe: A Case Report

Human allogeneic bone marrow-derived mesenchymal stem cell therapy for cerebellar ataxia: A case report

To date, there is no curable treatment option for non-hereditary degenerative cerebellar ataxia. Here we report the case of a patient with sporadic adult-onset ataxia (SAOA) who underwent allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy via the intrathecal route.

The Interdisciplinary Stem Cell Institute's Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases.

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

Autologous bone marrow derived mesenchymal stem cell therapy for osteonecrosis of femoral head: A systematic overview of overlapping meta-analyses

Study designSystematic Review. ObjectivesWe performed this systematic overview on the overlapping meta-analyses that analyzed autologous bone marrow-derived mesenchymal stem cell(BM-MSC) therapy along with core decompression(CD) for the management of osteonecrosis of the femoral head(ONFH) and identify which study provides the current best evidence on the topic and generate recommendations for the same. Materials and methodsWe conducted independent and duplicate electronic database searches in PubMed, Web of Science, Embase, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects till September 2020 for meta-analyses that analyzed the efficacy of BM-MSC therapy along with CD for ONFH. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades. We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation. Results6 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 4 to 9 (mean:7) and all the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The current best evidence showed that utilization of BM-MSC therapy along with CD for ONFH resulted in significant improvement in Harris hip scores at 12 and 24 months along with a significant reduction in the necrotic area of the femoral head and the rate of conversion to total hip arthroplasty(THA) without a significant rise in adverse events due to the procedure. ConclusionBased on this systematic overview, we give a Level II recommendation that BM-MSC therapy is more efficacious along with CD in the management of ONFH compared to CD alone. BM-MSC therapy provides better pain relief with significant functional improvement and delaying the collapse of the femoral head thereby preventing further treatment such as THA.

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration

Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs.

Efficacy of Stem Cell Therapy for Tendon Disorders: A Systematic Review.

Background:Stem cell therapy is an emerging treatment for tendon disorders.Purpose:To systematically review the efficacy of stem cell therapy for patients with tendon disorders.Study Design:Systematic review; Level of evidence, 4.Methods:MEDLINE/PubMed, EMBASE, CINAHL, CENTRAL, PEDro, and SPORTDiscus; trial registers; and gray literature were searched to identify randomized controlled trials (RCTs) and non-RCTs, cohort studies, and case series with 5 or more cases. Studies investigating any type of stem cell therapy for patients with tendon disorders were eligible if they included patient-reported outcome measures or assessed tendon healing. Risk of bias was assessed through use of the Cochrane risk of bias tools.Results:This review included 8 trials (289 patients). All trials had moderate to high risk of bias (level 3 or 4 evidence). In Achilles tendon disorders, 1 trial found that allogenic-derived stem cells led to a faster recovery compared with platelet-rich plasma. Another study found no retears after bone marrow–derived stem cell therapy was used in addition to surgical treatment. There were 4 trials that studied the efficacy of bone marrow–derived stem cell therapy for rotator cuff tears. The controlled trials reported superior patient-reported outcomes and better tendon healing. A further 2 case series found that stem cell therapy improved patient-reported outcomes in patients with patellar tendinopathy and elbow tendinopathy.Conclusion:Level 3 evidence is available to support the efficacy of stem cell therapy for tendon disorders. The findings of available studies are at considerable risk of bias, and evidence-based recommendations for the use of stem cell therapy for tendon disorders in clinical practice cannot be made at this time. Stem cell injections should not be used in clinical practice given the lack of knowledge about potentially serious adverse effects.

Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients.

Neurological disorders, including minimally conscious state (MCS), may be associated with the presence of high concentrations of reactive oxygen species within the central nervous system. Regarding the documented role of mesenchymal stem cells (MSCs) in oxidative stress neutralization, the aim of this study is to evaluate the effect of bone marrow-derived MSC (BM-MSC) transplantation on selected markers of oxidative stress in MCS patients. Antioxidant capacity was measured in cerebrospinal fluid (CSF) and plasma collected from nine patients aged between 19 and 45 years, remaining in MCS for 3 to 14 months. Total antioxidant capacity, ascorbic acid and ascorbate concentrations, superoxide dismutase, catalase, and peroxidase activity were analyzed and the presence of tested antioxidants in the CSF and plasma was confirmed. Higher ascorbic acid (AA) content and catalase (CAT) activity were noted in CSF relative to plasma, whereas superoxide dismutase (SOD) activity and total antioxidant capacity were higher in plasma relative to CSF. Total antioxidant capacity measured in CSF was greater after BM-MSC transplantations. The content of ascorbates was lower and CAT activity was higher both in CSF and plasma after the administration of BM-MSC. The above results suggest that MSCs modulate oxidative stress intensity in MCS patients, mainly via ascorbates and CAT activity.

Intrauterine Infusion of Human Platelet-Rich Plasma Improves Endometrial Regeneration and Pregnancy Outcomes in a Murine Model of Asherman's Syndrome.

Asherman’s syndrome (AS) is characterized by intrauterine adhesion or fibrosis resulting from damage to the endometrium, often leading to amenorrhea, infertility, or recurrent pregnancy loss. Although various therapeutic strategies for AS have been proposed, the options remain limited. New strategies such as bone marrow-derived mesenchymal stem cell (BM-MSC) therapy aim to potentiate the intrinsic capacity of endometrial regeneration. However, BM-MSC therapy has not been widely adopted mainly because it involves invasive and expensive procedures such as bone marrow biopsy and cell storing. On the other hand, platelet-rich plasma (PRP) is considered safe and affordable because it involves the less invasive procedure of blood collection from peripheral veins to produce PRP. To assess the effectiveness of human PRP infusion for endometrial regeneration, we established a murine model of injury-induced AS and evaluated endometrial morphology, expression of fibrosis-related factors, implantation sites (IS), and pregnancy outcomes associated with human PRP treatment. We found that treatment with human PRP was associated with improved endometrial morphology, reduced degree of fibrosis, and down-regulated expression of fibrosis-related factors in murine model of AS. Furthermore, human PRP treatment was associated with a higher number of IS and live-births. Our results suggest that human PRP treatment may become a valuable strategy to promote the regeneration of damaged endometrium and thus improve fertility and pregnancy outcomes in clinical practice.

Autologous Stem Cell Therapy for Cerebral Palsy

Introduction: We describe treatment of Cerebral Palsy with adult stem cells derived from bone marrow and fat of the same patient. Adult stem cells are of two types, the mesenchymal and haemopoietic stem cells which have potential to duplicate, indefinitely produce 50 types of growth factors that repair and regenerate tissues in an epigenetic manner. Every organ has its own stem cells, for example kidney stem cells, liver stem cells, etc. When specialized cells in an organ get damaged, the local stem cells come forward and get differentiated into specialized cells and the tissue damage is replenished. But when the stock of this reserve of local stem cell is over, the organ starts failing. In autologous stem cell therapy, we harvest stem cells from other healthy organs like fat and bone marrow which have abundant stem cells and put them into the diseased organ. Adult stem cells differentiate into neurons in vitro when added with nerve growth factor which is present in every nerve tissue. Our stem cell research was done by following all the guidelines set at national and international level. In India the incidence of cerebral palsy is around 5/1000 live births. In cerebral Palsy the upper motor neuron is weak, hence the lower motor neuron becomes hyper active leading to spasticity. The treatment involves mainly physiotherapy and prognosis is poor. Physiotherapy is a palliation and does not repair damage in the brain. The conventional therapy has failed to give any satisfactory results in these children hence something new needs to be done. Materials and Methods: In last 2 years we did stem cell therapy for 21 cases of CP in our center with age of 9 months to 17 years. Out of 21 cases of CP, 7 (33.3%) cases had quadriplegia, 6 (28.57%) paraplegia and 1 (4.76%) monoplegia, 2 (9%) hypotonic, 5 (23.8%) hemiplegia, 4 (19.04%) with mental retardation and 3 (14.28) had features of ADHD and Autism. 18 patients had squint in the eyes, 8 patients had food regurgitation and drooling of saliva, 2 patients had audiovisual impairment, 3 patients had bronchial asthma and one patient had menstrual irregularity. 26 cases were put as control with age range of 9 months to 19 years. 9 (34.61%) patients had quadriplegia, 8 (30.76%) paraplegia and 3 (11.53) had monoplegia, 3 (11.53%) hypotonic, 5 (19.23) with mental retardation and 6 (23.07) had features of ADHD and autism. 21 patients had squint in the eyes, 11 patients had food regurgitation and drooling of saliva, 4 patients had audiovisual impairment, 5 patients had bronchial asthma in the control group. 11 patients were subjected to adipose tissue derived stem cell therapy and 10 with bone marrow derived stem cell therapy. All patients were examined at 3 monthly intervals. Maximum follow up was 2.5 years and minimum of one year. Results: The results of bone marrow derived stem cells and adipose tissue derived stem cells were almost the same. Results took 3 months to appear and positive outcome came till one year since therapy. The spasticity was significantly reduced in 15 out of 18 patients in 6 months. Out of 18 patients who had squint, it was regressed completely in 12 (66.66%) patients and partially in 3 (16.66%) in 6 months’ time. 8 patients had faulty deglutition and 75% of them had 90% reg

Autologous Bone Marrow-Derived Stem Cell Therapy for Asherman's Syndrome and Endometrial Atrophy: A 5-Year Follow-up Study.

Background:Based on the role of bone marrow (BM) stem cells in regeneration of endometrium, refractory cases of Asherman's syndrome (AS) and endometrial atrophy (EA) may benefit with BM-derived intrauterine stem cell instillation. Aims and Objectives: To evaluate the role of BM-derived autologous stem cell therapy in endometrial regeneration and restoration of menstruation and fertility in refractory cases of AS and EA.Setting:This study was conducted at a tertiary care center.Design:This was a prospective, single-arm longitudinal study.Materials and Methods:Twenty-five cases with refractory AS or EA were included. BM-derived mononuclear stem cells were instilled into the subendometrial zone followed by oral estrogen therapy for 3 months. Menstrual flow and endometrial thickness (ET) were assessed at 3, 6, and 9 months and 5 years.Results:Statistical analysis was carried out using statistical software STATA version 12.0. Mean prestem cell transfer ET (mm) was 3.3 ± 1.0. At the end of 3 months, there was a significant increase in ET (mm) to 5.1 ± 1.9 (P = 0.001), but there was no significant change at 6 months (5.6 ± 1.5; P = 0.164), at 9 months (6.1 ± 1.7; P = 0.135), or at the end of 5 years. Six of the seven amenorrheic patients resumed menses. Three patients had a successful pregnancy outcome.Conclusion:Intrauterine stem cell treatment is a promising novel approach for refractory cases of AS and EA.

Bone Marrow Mesenchymal Stem Cell Therapy and Related Bone Marrow-Derived Orthobiologic Therapeutics.

The purpose of the current article is to review the available literature related to bone marrow-derived mesenchymal stem cell therapy in the management of musculoskeletal pathologies and demonstrate the critical need for additional well-designed clinical studies. In recent years, there has been a rapid increase in interest regarding the use of bone marrow-derived mesenchymal stem cells in the treatment of musculoskeletal injury and disease. The clinical use of BM-MSCs and other forms of stem cell therapy has far outpaced the basic and translational science evidence required to elucidate the potential efficacy of this orthobiologic treatment approach. Early studies have demonstrated potential clinical benefit of utilizing bone marrow-derived mesenchymal stem cell therapy in the management of knee osteoarthritis, focal chondral lesions, shoulder pathology including rotator cuff tears and glenohumeral arthritis, and degenerative disk disease in the spine. To date, most published studies are small case series often lacking a control group or a standardized method of treatment. Bone marrow-derived mesenchymal stem cell therapy is becoming an increasingly common treatment for musculoskeletal injuries and disease. Although early clinical studies have shown promising outcomes, methodological flaws and lack of standardization among trials have limited the conclusions that can be drawn from the existing literature. A better understanding of the underlying mechanism of action and more carefully designed clinical trials will help reveal the efficacy and utility of BM-MSCs as a treatment modality for various orthopedic pathologies.

The Anti-fibrotic and Anti-inflammatory Potential of Bone Marrow-Derived Mesenchymal Stem Cells and Nintedanib in Bleomycin-Induced Lung Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive lung damage. Tyrosine kinase inhibitors are approved to treat people with IPF while bone marrow-derived mesenchymal stem cell therapy was previously suggested to inhibit pulmonary fibrosis through the alveolar epithelial cell repair. The present study aimed to evaluate the anti-inflammatory and anti-fibrotic effect of the bone marrow-derived mesenchymal stem cell (BM-MSC) therapy in comparison with nintedanib, a tyrosine kinase inhibitor, on improving survival in bleomycin-induced lung fibrosis in rats. Moreover, the combined therapy of BM-MSCs and nintedanib will be evaluated. In the present study, IPF was induced through intra-tracheal instillation of bleomycin (5mg/kg) in rats then treatments were administered 14days thereafter. Nintedanib (100mg/kg, I.P.) was administered daily for 28days, while BM-MSCs were injected once intravenously in tail vein in the dose 1 × 106cells/ml/rat. In the present study, both treatment regimens effectively inhibited lung fibrosis through several pathways, suppressing tumor growth factor-β (TGF-β)/SMAD3 expression which is considered the master signaling pathway. Nintedanib and BLM-MSCs exerted their anti-inflammatory effect through minimizing the expression of TNF-α and IL-6. In addition, the histopathological examination of the lung tissue showed a significant decrease in the alveolar wall thickening, in the inflammatory infiltrate, and in the collagen fiber deposition in response to either nintedanib or BM-MSC and their combination. In conclusion, the therapeutic pulmonary anti-fibrotic activity of nintedanib or BM-MSC is mediated through their anti-inflammatory properties and inhibition of SMAD-3/TGF-β expression.

Bone Marrow Mesenchymal Stem Cell with Up-Regulation of MicroRNA-206 in the Treatment of Bronchopulmonary Dysplasia in Newborn Mice

Background:: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm neonates with a few therapeutic options. Our previous studies suggested that bone marrow-derived mesenchymal stem cell (BMSC) therapy is effective in the treatment of BPD in mouse models. Furthermore, microRNA-206 (miR-206) suggested having a correlation with BPD by regulating the expression of fibronectin 1 (FN1). Objectives:: The aim of this study was to characterize the role of BMSCs with the up-regulation of miR-206 in the treatment of BPD in newborn mice. Methods: The BPD mouse model was induced by 60% oxygen. BMSCs transfected with miR-206 or negative control (NC) plasmid were administered on postnatal day 7 (P7) and every following week through an intraperitoneal injection (105 cells/animal) until P35. The mice were weighed and their lungs were weighed and prepared for histology. The expression levels of miR-206, FN1, and pulmonary surfactant-associated protein-C (SP-C) were determined through the quantitative polymerase chain reaction and under the immunofluorescence. The protein expression levels of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) were determined by ELISA. Results: BMSCs with up-regulation of miR-206 reduced the degrees of pulmonary edema, improved pulmonary architecture, and attenuated inflammation in BPD mice compared to the NC plasmid group. Furthermore, the up-regulation of miR-206 in BMSCs down-regulated the expression levels of TGF-β and IL-6 in plasma samples and of SP-C and FN1 in the lung tissue of BPD mice. Conclusions: BMSCs with up-regulation of miR-206 are effective in the treatment of BPD in newborn mice, and the study introduced a novel idea for the treatment of BPD.

Bone Marrow-Derived and Adipose-Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review.

Regenerative medicine in the context of musculoskeletal injury is a broad term that offers potential therapeutic solutions to restore or repair damaged tissue. The current focus in recent literature and clinical practice has been on cell based therapy. In particular, much attention has been centered on autologous bone marrow concentrate and adipose-derived mesenchymal stem cells (MSCs) for cartilage and tendon disorders. This article provides an overview of MSC-derived therapy and offers a comprehensive review of adipose- and bone marrow-derived MSC therapy in primary knee osteoarthritis. LEVEL OF EVIDENCE: IV.

3040 - Five Year Follow Up of Chronic Spinal Cord Injury Patients Receiving Autologous Bone Marrow-Derived Mesenchymal Stem Cell Therapy Combined with Physical Therapy

3040 - Five Year Follow Up of Chronic Spinal Cord Injury Patients Receiving Autologous Bone Marrow-Derived Mesenchymal Stem Cell Therapy Combined with Physical Therapy