Autologous Bone Marrow-derived Stem Cells Research Articles

Autologous bone marrow derived mesenchymal stem cells are safe for the treatment of Achilles tendinopathy

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5–19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.

Autologous bone marrow-derived mesenchymal stem cells and endothelial progenitor cells transplantation showed potential benefits for type 2 diabetes mellitus Filipino patients: a case series

Autologous bone marrow-derived mesenchymal stem cells and endothelial progenitor cells transplantation showed potential benefits for type 2 diabetes mellitus Filipino patients: a case series

Cell-based tissue engineered flexor tendon allograft: A canine in vivo study.

This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.

Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Effects of Timing on the Efficacy of Stem Cell Transplantation after Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the blocking of coronary arteries that prevents oxygenated blood from reaching the heart tissues, resulting in damage to the myocardium and affecting heart function. This condition affects millions of people every year and is detrimental to their quality of life. Several clinical trials have investigated the efficacy of using bone marrow-derived stem cells (BMSCs) to improve heart function after AMIs. However, different variables could impact the results of the trials, one of them being the injection time of cell therapy after reperfusion. This paper aims to investigate the short-term effects of timing on the efficacy of bone marrow-derived mononuclear cell transplantation after acute myocardial infarction. A systematic literature search of PUBMED, EMBASE, European Society of Cardiology, and American Heart Association databases was made on randomized controlled trials with at least 3-month follow-up data for patients with AMI undergoing percutaneous coronary intervention (PCI) and receiving intracoronary autologous BMSC transfer subsequently. A total of 12 trials with 1061 patients were selected for analysis. Compared to baseline level, BMSC transfer within 24 hours of PCI significantly improved left ventricular ejection fraction (LVEF; 3.44% increase, 95% confidence interval [CI]: 2.20%-4.68%, P< 0.00001). The “3-7 days after PCI” subgroup also showed notable improvements in LVEF (LVEF; 2.52% increase, 95% confidence interval [CI]: 1.01%-4.04%, P = 0.001). However, in the subgroups that received BMSC transplantation either 7-14 days after PCI or later than 15 days after PCI, there was no significant effect on treatment outcome.

Stem Cell Therapy in Stargardt Disease: A Systematic Review.

This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.

Long-term survival benefits of intrathecal autologous bone marrow-derived mesenchymal stem cells (Neuronata-R®: lenzumestrocel) treatment in ALS: Propensity-score-matched control, surveillance study.

Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel. A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment. Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration. The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.

Acellular Biomaterials Associated with Autologous Bone Marrow-Derived Mononuclear Stem Cells Improve Wound Healing through Paracrine Effects

Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV-injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-β was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-β. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.

Safety and efficacy of internal carotid artery infusion of autologous bone marrow-derived stem cells in subacute middle cerebral artery infarct

Objective: To evaluate the safety and the efficacy of internal carotid artery (ICA) infusion of autologous bone marrow-derived stem cells (BMSC) in subacute middle cerebral artery (MCA) infarct. Subject and method: A prospective, open-label, non-randomized was conducted in patients with MCA infarct, within 7-40 days from onset. Sixty-two patients satisfying the inclusion criteria were enrolled and allocated into either BMSC group (n = 31) or control group (n = 31). Follow-ups were performed at 6 months and 1 year after therapy. Adverse events were noted to conclude safety outcome. The primary efficacy outcomes were percentages of recovered patients with a score of 0 to 2 on the modified Rankin Scale (mRS). The secondary efficacy outcomes were evaluated by the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Brunnstrom stages of hand (BRS-H), and infarct volume on head MRI. Result: There were no significant differences in the percentages of noted adverse events. The percentages of the mRS 0-2 in BMSC group were remarkably higher as compared to control group at both 6-month and 1-year follow-up, but not statistically significant (25.8% vs 6.9%, p=0.08 and 26.7 vs 9.7, p=0.1, respectively). BI at 6 months was significantly better in the BMSC group, however no significant differences on other secondary efficacy measures. Conclusion: ICA infusion of BMSC was safe and tolerated in patients with subacute MCA infarct. Although the difference in the primary efficacy outcomes was not statistically significant, a favorable trend was found in BMSC group representing by the BI at 6 months and the percentages of mRS 0-2 at both main follow-ups.

Significant improvement of Barthel index scores in patients with subacute middle cerebral artery infarct after intravenous autologous bone marrow-derived stem cells infusion

Objective: To assess the safety and the efficacy of intravenous infusion of autologous bone marrow-derived stem cells (BMSC) in subacute middle cerebral artery (MCA) infarct. Subject and method: A prospective, open-label, non-randomized was performed in patients with MCA infarct, within 7-40 days from onset. Sixty-three patients, satisfying the inclusion criteria, were enrolled, and allocated into the IV-BMSC group (n = 32) or into control group (n = 31). Main follow-ups were at 6 months and 1 year after therapy. Adverse events were noted to conclude safety outcome. The primary efficacy outcomes were proportions of patients achieving a score of 0 to 2 on the modified Rankin Scale (mRS). The secondary efficacy outcomes were evaluated by the National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI), Brunnstrom stages of hand (BRS-H), and infarct volume on head MRI. Result: There were no statistically significant differences in the rates of noted adverse events. There were no significant differences between the two groups on the proportions of the mRS 0-2 at both 6-month and 1-year follow-up (3.2% vs 6.9% with p=0.6, and 6.9 vs 9.7 with p=1.0, respectively). The improvement of BI at 6 months was significantly better in the IV-BMSC group compared to control group, however no significant differences on other secondary efficacy measures. Conclusion: Intravenous infusion of BMSC was safe in patients with subacute MCA infarct. Although the difference in the primary efficacy outcomes was not statistically significant, a favorable secondary outcome was observed in IV-BMSC group, presenting by the statistically significant improvement of the Barthel index at 6-month follow-up.

Treatment of racehorse superficial digital flexor tendonitis: A comparison of stem cell treatments to controlled exercise rehabilitation in 213 cases.

Overstrain of the superficial digital flexor tendon (SDFT) is a common Thoroughbred racehorse limb injury requiring treatment. To determine whether treatment of SDFT lesions in flat Thoroughbred racehorses with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) or allogenic adipose-derived mesenchymal stem cells (A-MSCs) is associated with improved likelihood of returning to racing, when compared to racehorses managed with a controlled exercise rehabilitation program (CERP) alone. Retrospective cohort study combining clinical treatment records with race records. A total of 213 Thoroughbred racehorses were identified. All were prescribed the same 12-month CERP and 66 also received intralesional BM-MSC and 17 A-MSC treatment. Follow-up was a minimum of 2 years after return to full race training. Multivariable logistic regression models were used to investigate associations between the treatments and the likelihood of returning to racing and completing five or more (C5+) races post-injury. Compared to CERP alone, BM-MSC treatment was associated with increased odds of returning to racing (OR 3.19; 95% CI 1.55-6.81) and C5+ races post-injury (OR 2.64; 95% CI 1.32-5.33). Older age and increasing lesion length were associated with a reduced likelihood of returning to racing. Male sex and increased number of pre-injury starts were associated with increased odds of returning to racing. There was no observed increased likelihood of return to racing or C5+ races associated with treatment with A-MSCs compared to CERP alone. Due to the retrospective nature of the study it was not possible to ascertain how strictly the CERP was followed. Due to the novelty of the method, the A-MSC treatment group included a limited number of horses. In the study population, intralesional BM-MSC treatment was significantly associated with an increased likelihood of returning to racing and C5+ races post-injury compared to CERP alone. Intralesional A-MSC showed no significant association between treatment and the two investigated outcomes.

PROSPECTIVE SINGLE CENTER ANALYSIS OF OUTCOME STEM CELLS TRANSPLANTS IN PATIENTS WITH CEREBRAL PALSY.

Aim: To evaluate efficacy and safety of autologous bone marrow-derived mononuclear stem cell transplantation intrathecal in children with cerebral palsy. Materials and Methods: 35 children have levels I-V cerebral palsy aged 8-months to 8-years-old were enrolled from September (2021-2022) at Iraqi private hospital. Gross Motor Function was assessed by a pediatrician and neurologist specialist, 5 mcg/kg/day of G-CSF subcutaneous single injection daily for three consecutive days. Bone marrow harvested from posterior iliac crest under light general anesthesia. Bone marrow mononuclear cells (BMMNCs) separation was performed using density gradient centrifugation with Ficoll, the cell viability checked by propidium iodide dye in a TALI machine (Invitrogen) in average 98%. The viable BMMNCs injected intrathecal in L4-L5 over a period of 5-10 min. Results: Males accounted for 57.14% (20/35) while female 42.86% (15/35), and main neurological symptoms included spastic disorder spastic disorder (quadriplegia 24 (68.6), tetraplegia 2 (5.7), diplegia 5 (14.28), hemiplegia4 (11.42)). Gross Motor Function Classification System and Gross Motor Function Measure-66 (GMFM-66) showed II 10 (28.58), III 11(31.42) and IV 14 (40). On mean follow-up of 3 months post-stem cell transplant improvement was observed in 80% cases. The improvement showed in gross motor function (6/8) p=0.01, and speech (2/4) p=0.04, neck holding (5/5) p=0.0003, sitting balance (4/4) p=0.04, postural tone (5/5) p=0.0003, as well as significant reduction in seizure frequency (2/3) p=0.04 and improvement in cognition (6/7) p=0.01 were observed. Conclusion: Stem cell therapy for cerebral palsy shows a significant positive effect on the gross motor function, without long adverse effects.

Randomized control trial of mesenchymal stem cells versus hyaluronic acid in patients with knee osteoarthritis - A Hong Kong pilot study.

ObjectiveThis pilot study evaluated the efficacy of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) versus hyaluronic acid (HA) in surgically naïve patients with knee osteoarthritis (OA).MethodsSingle-centre, single-blind randomized study of patients with knee OA. Twenty patients were randomized into groups of 10 each for intra-articular injection of cultured BM-MSCs (6 ​ml of BM-MSCs at 1 ​× ​106 ​cells/mL) or HA (6 ​ml). Clinical assessments of pain, quality of life, radiographic imaging, and magnetic resonance imaging (MRI) compositional change were performed at baseline and 12 months follow-up.ResultsCompared with HA, BM-MSCs injection resulted in significant improvement in qualify of life and reduction in pain as reflected by visual analogue scale (VAS) pain score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and 36-Item Short Form Survey (SF-36) score collectively. T2-relaxation time tended to decrease more in the BM-MSCs group with a 38 ​± ​24.0% reduction in 6 out of 10 BM-MSC participants; while there was only a 12 ​± ​7.9% reduction in 4 out of 10 HA participants at the end of follow-up. The remaining participants showed either no response or had relaxation time increased on MRI assessment.ConclusionsThis pilot study found that autologous BM-MSCs significantly reduced pain, improved functional assessment score, and improved quality of life parameters comparing with HA at one year follow-up. Further clinical trial with larger sample size and longer follow up duration is warranted.The Translational Potential of this ArticleThis pilot RCT demonstrated the feasibility and potential effectiveness of BM-MSCs advanced therapy for patients with knee OA compared to HA injection. Further multi-center clinical trial with a larger sample size and longer follow up duration in accordance with latest regulatory guidelines is warranted to ascertain the long term safety and effectiveness of MSCs therapy for cartilage regeneration in OA.RegistrationThe study was registered in the Centre for Clinical Research Biostatistics - Clinical Trials Registry (CUHK_CCT00469).

Direct pulp capping with autologous bone marrow derived stem cells in dogs.

Bone-marrow derived stem cells (BMSCs) can differentiate into several mesenchymal cell lines that are suitable for bone and dental tissue engineering. This study was aimed to assess the efficacy of cell therapy in direct pulp capping (DPC) of canine teeth using autologous BMSCs along with collagen/hydroxyapatite hybrid scaffold in terms of the quantity and quality of calcified bridge formation. The teeth were randomly divided into three groups of DPC with mineral trioxide aggregate (MTA), hydroxyapatite/collagen hybrid scaffold alone and BMSCs with hydroxyapatite/collagen hybrid scaffold. DPC was performed under general anesthesia in cavities prepared on the buccal surfaces of mandibular and maxillary premolars of the same dogs from which, stem cells had been isolated. All cavities were then restored with light-cure resin modified glass ionomer cement. Histomorphometric assessments after 12 weeks showed formation of dentinal bridge following DPC with BMSCs and MTA. The efficacy of MTA for calcified bridge formation following DPC was significantly higher than that of BMSCs plus hybrid scaffold. According to the present study, we concluded DPC using BMSCs and hybrid scaffold did not provide clinically noticeable results in canine patients.

Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial

BackgroundA single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.MethodsALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months.DiscussionLenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.Trial registrationClinicalTrials.govNCT04745299. Registered on Feb 9, 2021.Clinical Research Information Service (CRIS) KCT0005954. Registered on Mar 4, 2021.

The Emerging Role of Non-Coding RNAs in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Autologous bone marrow-derived mesenchymal stem cells (BMSCs) are more easily available and frequently used for bone regeneration in clinics. Osteogenic differentiation of BMSCs involves complex regulatory networks affecting bone formation phenomena. Non-coding RNAs (ncRNAs) refer to RNAs that do not encode proteins, mainly including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, transfer RNA-derived small RNAs, etc. Recent in vitro and in vivo studies had revealed the regulatory role of ncRNAs in osteogenic differentiation of BMSCs. NcRNAs had both stimulatory and inhibitory effects on osteogenic differentiation of BMSCs. During the physiological condition, osteo-stimulatory ncRNAs are upregulated and osteo-inhibitory ncRNAs are downregulated. The opposite effects might occur during bone degenerative disease conditions. Intracellular ncRNAs and ncRNAs from neighboring cells delivered via exosomes participate in the regulatory process of osteogenic differentiation of BMSCs. In this review, we summarize the recent advances in the regulatory role of ncRNAs on osteogenic differentiation of BMSCs during physiological and pathological conditions. We also discuss the prospects of the application of modulation of ncRNAs function in BMSCs to promote bone tissue regeneration in clinics.

Exosomes Derived From CTF1-Modified Bone Marrow Stem Cells Promote Endometrial Regeneration and Restore Fertility.

Background: Thin endometrial tissue is a leading cause of embryo transfer failure, potentially contributing to sustained infertility and associated adverse outcomes. The application of exosomes derived from autologous or allogeneic bone marrow-derived stem cells (BMSCs) has been used to promote uterine repair following injury, and there is also prior evidence that stem cell transplantation can bolster fertility. Genetic modifications represent a primary approach to enhancing exosomal therapy strategies. The present study thus explored the effects of Cardiotrophin-1 (CTF1)-modified BMSCs-exo on fertility-related outcomes. Methods: An adenoviral vector was used to generate CTF1-overexpressing BMSCs (C-BMSCs), after which exosomes were isolated from control BMSCs (BMSC-exos) and C-BMSCs (C-BMSC-exos). The angiogenic effects of C-BMSC-exo treatment were assessed through analyses of endothelial cell proliferation and tube formation. Model rats exhibiting endometrial thinning were administered C-BMSCs-exo, after which the effects of such treatment were assessed through H&E staining, Masson’s trichrome staining, and immunofluorescence analyses. The mechanistic basis for the proangiogenic effects of CTF1 as a driver of endometrial regeneration was additionally explored. Results: C-BMSC-exo treatment of HUVECs was associated with enhanced neovascularization, as evidenced by improved in vitro proliferation, migration, and tube formation. Importantly, such treatment was also linked to tissue regeneration, neovascularization, and the suppression of localized tissue fibrosis in vivo. Regenerated endometrial tissue exhibited higher embryo receptivity and was associated with higher birth rates in treated rats. The upregulation of the JAK/PI3K/mTOR/STAT3 signaling pathways in C-BMSC-exo-treated rats may underscore the mechanistic basis whereby CTF1 can positively impact endometrial angiogenesis and regeneration. Conclusion: Our data suggest that exosomes produced by CTF1-modified BMSCs can more effectively promote the regeneration of endometrial and myometrial tissues, driving neovascularization in a manner that improves endometrial receptivity in a rat model system, highlighting the therapeutic promise of this approach for patients diagnosed with endometrial thinning.

Role of bone marrow-derived mesenchymal stem cells in treatment avascular necrosis of femoral head

Avascular necrosis (AVN) of the femoral head (FH) is a debilitating and painful disease with multiple etiologic risk factors head shows an increasing tendency and most commonly affects younger or middle-aged adults. Fifty patients (55 hips) with stage I, II or III avascular necrosis of femoral head were treated by autologous Bone marrow-derived mesenchymal stem cells injection. The patients were followed up clinically and radiologically for a minimum of 2 years at baseline, three, six, 12, and 24 months. The functional outcome was assessed in terms of Harris hip score, and disease progression was assessed radiologically by comparing the preoperative and follow-up MRI at the end of 2 years. On 2-year follow-up, there was considerable improvement in the hip function as measured by the Harris hip score (p = 0.041). On MRI, there was a decrease in the size of the lesion in group A (p = 0.03). Our findings showed that autologous Bone marrow-derived mesenchymal stem cells in avascular necrosis of femoral head is a safe and effective procedure and has better outcome.

Role of bone marrow-derived mesenchymal stem cells in treatment avascular necrosis of femoral head

Avascular necrosis (AVN) of the femoral head (FH) is a debilitating and painful disease with multiple etiologic risk factors head shows an increasing tendency and most commonly affects younger or middle-aged adults. Fifty patients (55 hips) with stage I, II or III avascular necrosis of femoral head were treated by autologous Bone marrow-derived mesenchymal stem cells injection. The patients were followed up clinically and radiologically for a minimum of 2 years at baseline, three, six, 12, and 24 months. The functional outcome was assessed in terms of Harris hip score, and disease progression was assessed radiologically by comparing the preoperative and follow-up MRI at the end of 2 years. On 2-year follow-up, there was considerable improvement in the hip function as measured by the Harris hip score (p = 0.041). On MRI, there was a decrease in the size of the lesion in group A (p = 0.03). Our findings showed that autologous Bone marrow-derived mesenchymal stem cells in avascular necrosis of femoral head is a safe and effective procedure and has better outcome.

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.