Autologous Bone Marrow-derived Stem Cells Research Articles

Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation for Decompensated Post-Hepatitis B Cirrhosis: A Case Report

End-stage liver disease (ESLD) represents the terminal phase of chronic liver injury, characterized by overt clinical manifestations and severe complications that significantly impair the quality of life. The condition often culminates in a variety of symptoms, including jaundice, ascites, and hepatic encephalopathy, which reflect the liver's inability to perform its essential functions. Liver transplantation remains the definitive treatment for ESLD; however, limitations in donor organ availability necessitate exploration of alternative therapeutic strategies. we present a case of a 71-year-old Asian male with decompensated post-hepatitis B cirrhosis, who had a one-year history of hematemesis and melena. Endoscopic evaluation confirmed the presence of esophageal-gastric varices, further corroborating portal hypertension and hypersplenism. This patient underwent treatment with autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation. Following the procedure, the patient demonstrated significant clinical improvement, suggesting the safety and potential feasibility of BM-MSC transplantation for patients with ESLD. The field of BM-MSC transplantation has witnessed significant progress in recent years, emerging as a promising therapeutic approach for ESLD. This innovative treatment modality harnesses the regenerative capabilities of stem cells to promote liver repair and function. Notably, BM-MSCs possess immunomodulatory properties that may mitigate inflammation and fibrosis in the liver, thereby addressing some of the underlying pathophysiology associated with ESLD. This case presentation highlights the potential application of BM-MSC therapy in patients with decompensated cirrhosis. The findings underscore the need for further research and refinement of clinical application techniques to fully realize the broad therapeutic possibilities of BM-MSC transplantation for ESLD. As we advance our understanding of stem cell therapies, it is crucial to conduct larger studies to evaluate long-term outcomes and establish standardized protocols for treatment.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells in the Reversal of Unobstructed Azoospermia in Rats.

Non-obstructive azoospermia (NOA) is an important cause of male infertility. This study is being proposed to assess the efficacy of autologous bone marrow-derived mesenchymal stem cells (MSCs) in the reversal of busulfan-induced NOA in rats. Twenty adult 3-month-old male rats were divided into two groups: a control group and a study group. In the study group, bone marrow was aspirated to culture MSCs. NOA was created by stopping endogenous spermatogenesis in all the animals by injecting two doses of busulfan 10 mg/kg body weight with a 3week interval. Four weeks after the last dose of busulfan, two animals were euthanized and the testes were studied histologically to confirm complete azoospermia. In the study group, five million MSCs in 1 mL normal saline were injected into seminiferous tubules; and in the control group, 1 mL of normal saline was injected. After 4weeks of MSC injection, all the rats were euthanized and epididymis tails and testes were harvested and sent for measurement of serological indices, including luminal, cellular, and total diameters, luminal, cellular, and cross-sectional areas, number of tubules per unit area of testis, numerical density of the tubules, and spermatogenesis index, pre- and post-MSC transplantation. The effect of busulfan on the testicular tissue was universally devastating. In the control group, there was variable length and width of markedly necrotic seminiferous tubules, whereas in the group treated with autologous bone marrow-derived MSCs there was variable height of germinal epithelium in seminiferous tubules, with active spermatogenesis, showing spermatogonia, spermatocytes, and sperm. MSC injection in the testis has the potential to reverse the testicular function of spermatogenesis after cytotoxic therapy. Human trials should be undertaken to confirm our findings and bring the results into clinical practice.

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.

Therapeutic Effect of Stem Cells from Different Sources on Diabetic Foot Ulcers: Systematic Review and Network Meta-Analysis.

To evaluate the efficacy of stem cell therapy from different sources on the ankle-brachial index, wound closure percentage, and wound closure time in the treatment of diabetic foot ulcers (DFUs). A literature search was conducted in PubMed, Embase, Cochrane Library's Central Register of Controlled Trials, and Web of Science, extending through June 29, 2023. Quality evaluation was done using the Cochrane's bias risk assessment tool (RoB 2.0). Employing a Bayesian approach, the statistical computations was executed with the JAGS software, leveraging the gemtc 0.8-2 and rjags 4-10 libraries, within the R environment 4.1.2. The included interventions came from peripheral blood, bone marrow, placenta, umbilical cord blood, adipose tissue, or others. A preliminary search identified 2286 articles, of which 23 randomized controlled trials met the inclusion criteria and were ultimately included. The analysis findings indicated that mesenchymal stem cells derived from the umbilical cord (HUCMSCs) led to a notable enhanced the ankle-brachial index in patients with DFUs compared to standard treatment (MD: 0.2; 95% CI [0.01, 0.36]). HUCMSCs were found to be the optimal therapeutic approach for enhancing the ankle-brachial index (SUCRA = 82.7%). Research on the wound closure percentage revealed that compared to platelet-rich plasma (PRP), processed microvascular tissue (PMVT), peripheral blood stem cells (PBSCs), microfragmented adipose tissue (MFAT), autologous bone marrow-derived stem cell therapy (ABMSCT), adipose-derived stem cells (ASCs), and dehydrated human umbilical cord allograft (EpiCord), Huoxue Shengji Decoction (HXSJD) + ABMSCT (H_Group_hematopoietic) significantly increased the wound closure percentage in DFU patients (P < 0.05). According to the SUCRA ranking, HXSJD + ABMSCT was the best therapeutic method to increase the percentage of wound closure (SUCRA = 93.8%). This study employed a network meta-analysis method, combining direct and indirect comparisons, to analyze the latest clinical data and concluded that umbilical cord mesenchymal stem cells and the combination of HXSJD + autologous bone marrow hematopoietic stem cell treatment as adjunctive therapies for DFUs may have beneficial effects. Future research needs to focus on this.

Stem cell therapy in diabetic men with erectile dysfunction: a 24-month follow-up of safety and efficacy of two intracavernous autologous bone marrow derived mesenchymal stem cells injections, an open label phase 2 clinical trial

BackgroundRecently we reported results of phase 1 pilot clinical trial of 2 consecutive intracavernous (IC) injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (DM-ED). In phase 2 of this study our aim is to evaluate long term safety and efficacy of IC injections of BM-MSC on additional eight patients with DM-ED.ResultsEach patient received 2 consecutive IC injections of BM-MSC and evaluated at 1, 3, 6, 12, and 24-month time points. Primary outcome was the tolerability and safety of stem cells therapy (SCT), while the secondary outcome was improvement of erectile function (EF) as assessed using the International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS) questionnaires, and Color Duplex Doppler Ultrasound (CDDU). IC injections of BM-MSCs was safe and well-tolerated. Minor local and short-term adverse events related to the bone marrow aspiration and IC injections were observed and treated conservatively. There were significant improvement in mean IIEF-5, EHS, all over the follow-up time points in comparison to the baseline. At 24-month follow up there were significant decline in the mean IIEF-5, and EHS compared to the baseline. The mean basal and 20-min peak systolic velocity was significantly higher at 3-month after the IC injections compared to baseline.ConclusionsThis phase 2 clinical trial confirmed that IC injections of BM-MSC are safe and improve EF. The decline in EF over time suggests a need for assessing repeated injections.Clinical trial registrationNCT02945462

Implantation of Culture-Expanded Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Osteonecrosis of the Femoral Head.

Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH. A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0years [interquartile range (IQR), 28.5-42.0], and the median follow-up period was 4.0years (IQR, 2.0-5.3). The median number of MSCs was 1.06 × 108. To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up. The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips. CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH.

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

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.

Clinical safety and therapeutic efficacy of autologous bone-marrow derived stem cells in restoring glycemic control and treating complications in diabetic patients

Diabetes is one of the most common chronic diseases worldwide, with around 537 million adults aged 20-79 living with the disease. It is a global epidemic and has a rapidly rising incidence. Traditional treatments for diabetes have limited efficacy in achieving long-term disease control. In recent years, the autologous infusion of bone marrow-derived mononuclear cells (BMMNC) has become a novel and effective therapeutic approach in treating autoimmune type 1 diabetes (T1DM). BMMNC contains two important types of stem cells, bone marrow-derived hematopoietic stem cells (BMHSC) and bone marrow-derived mesenchymal stem cells (BMMSC), which are currently used independently or coordinately in the treatment of T1DM. In this review, we summarize the clinical data concerning BMMNC, BMHSC, and BMMSC infusion in patients with diabetes (including type 1, type 2, and secondary diabetes) and diabetes-related complications. Research suggests that the autologous infusion of bone marrow stem cells is safe and effective, offering the potential to be widely used in patients with diabetes.

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&lt; 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.