Autologous Mesenchymal Stem Cells Research Articles

A pioneer surgical technique for isolated periodontal defects by “closed” retraction of the papilla: A feasibility study

AimA pioneer periodontal surgical approach employing the closed surgical technique (CST) in combination with the tissue-engineered biocomplex aimed to gain access to the osseous defect and improve soft tissue architecture.MethodsThe CST was applied in four systemically healthy periodontitis patients/defects who were followed for 12 months. It avoids papilla dissection and retraction of flaps in an open manner; thus, suturing is not required. It is designed for the reconstruction of residual isolated periodontal defects and is best indicated in the aesthetic region. It can be applied as a sole treatment approach to facilitate deep instrumentation of the defect, or it could be combined with subgingival application of regenerative materials. Hereby, the biocomplex was applied containing autologous alveolar bone marrow mesenchymal stem cells, seeded into collagen scaffolds, enriched with autologous fibrin/platelet lysate.ResultsThe CST minimized postoperative discomfort and led to improved treatment outcomes with probing pocket depth reduction [average (SD)] of 24.4% (18.5), gain in clinical attachment levels of 25.8% (20.1), and evidence of remineralisation of the alveolar crest.ConclusionThe CST is a tissue-friendly operation and facilitates subgingival application of biological agents via tunneling the soft tissues. However, surgical experience is required for nontraumatic manipulation of the gingival tissues during “closed” retraction of the flaps.Clinical trial registrationRegistered with Clinicaltrials.gov; ClinicalTrials.gov ID: NCT02449005.

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial.

BackgroundBrain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury.ObjectiveThe objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury.MethodsThe (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion.ResultsWe received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan.ConclusionsOur phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury.Trial RegistrationJapan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbcInternational Registered Report Identifier (IRRID)DERR1-10.2196/37898

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

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

The first experience of reproductive function restoration in patients with Asherman’s syndrome using autologous mesenchymal stem cells

The main goal of Asherman’s syndrome treatment is to restore the volume and shape of the uterine cavity, regenerate the endometrium and reproductive function. Recently, in addition to ultrasound diagnostics of intrauterine synechiae, office hysteroscopy is widely used. The most standardized stages of Asherman’s syndrome treatment are hysteroscopic dissection of the uterine cavity synechiae and endometrium re-adhesion prevention in the postoperative period, which is achieved by the introduction of the intrauterine device, anti-adhesive drugs or balloon catheters inserted intrauterinely. The main difficulties are to find effective ways to prevent adhesion that occurs after removal of mechanical means from the uterine cavity and ways to restore the endometrium morphology in patients wishing to achieve pregnancy. The most promising technique in this area is the use of autologous endometrial stem cells. Here is a case of treatment of a reproductive age patient with infertility and Asherman’s syndrome. The clinical case was a part of a clinical trial Clinical Trials.gov Identifier: NCT04675970. On the eve of the operative stage for uterine cavity synechiae separation 20.0 ml of venous blood was taken. Mesenchymal stem cells (MSCs) were isolated from the patient’s peripheral blood using the magnetic separation method of the autoMACS Pro Separator (Miltenyi Biotec). According to the international instructions, 6th passage MSCs were clinically used. Confirmation of belonging the derived cells to the MSCs group was performed using the set Bio-Techne FMC-020 (Great Britain). In addition, MSCs were differentiated to endometrial cells, which was confirmed using endometrial cell matching markers in generations P0-P3 (passage 0 – passage 3) with the MicroBead Kit (USA). The operative stage of treatment included office hysteroscopy, mechanical synechiolysis in the endocervix and endometrium and introduction of a silver-containing intrauterine device. Subendometrial injection of autologous endometrial MSCs was performed to restore the endometrium structure at the end of hysteroscopy. High dose adjuvant estrogen therapy followed for 3 weeks. Pregnancy was achieved spontaneously 2 years after the intervention. The patient gave birth to a full-term baby girl.The results of the clinical case indicate the prospects for the use of autologous blood stem cells converted into endometrial cells in the treatment of infertility in patients with CA in the absence of effect from previous attempts to restore fertility by traditional therapies.

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.

3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration

Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface. These scaffolds were tested in a rabbit rotator cuff injury model and the histological, radiological, and biomechanical changes were analyzed. The in vivo studies demonstrated that the scaffold with spatially differentiated autologous ADMSCs had a superior histological score and improved collagen organization when compared to acellular scaffolds and similar T2 value as the normal interface tissue. The biomechanical characterization demonstrated that the application of multilayered scaffolds improved the biomechanical properties of the tendon-to-bone interface at 12 weeks after rotator cuff reconstruction surgery, but the incorporation of autologous ADMSCs within the multilayered scaffolds showed a limited contribution. Thus, our work provides a 3D-bioprinting-based strategy with the application of autologous ADMSCs to reconstruct massive rotator cuff tendon tears.

The use of autologous mesenchymal stem cells in complications of diabetes mellitus, in particular diabetic retinopathy: inputs and insights

The review provided reveals the analysis of the available scientific literature on the feasibility of using cellular technologies, such as, autologous mesenchymal stem cells (MSCs) for diabetic retinopathy treatment. The results indicated the viability of cellular technologies in clinical ophthalmology with respect to anatomical features and immune privilege of the organ of vision. Additionally, feasibility, safety, and optimization of pathogenetic therapy for MSC transplantation expands the prospect of their use in late complications of type 1 and type 2 diabetes mellitus, in particular, diabetic retinopathy.

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration.

Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients’ sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.

Low-dose mesenchymal stem cell therapy for discogenic pain: safety and efficacy results from a 1-year feasibility study.

Aim:To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP).Methods:Nine participants with chronic LBP originating from single-level lumbar disc disease underwent intradiscal injection of 10 million ADMSCs with optional repetition after 6 months.Results:No unexpected or serious adverse events were recorded. Seven (78%) of participants reported reductions in pain 12 months after treatment. Five (56%) reported increased work capacity. Three (33%) reduced analgesic medication. Improvements in EQ-5D and Oswestry disability index results were observed. MRI demonstrated no further disc degeneration and improvements to annular fissures and disc protrusions.Conclusion:This study provides initial evidence of safety and efficacy of ADMSCs for discogenic LBP.

Hybrid SPECT/CT for Tracking of Mesenchymal Stem Cells after Intravenous and Intra-Thecal Administration in Acute Cervical Traumatic SpinalCord Injury

Introduction: Mesenchymal stem cells (MSCs) are a promising strategy for spinal cord repairafter traumatic spinal cord injury (tSCI), but their ability to migrate, engraft, and survive at injury sites has yet to be investigated in humans.Case Presentation: In this case report, using hybrid SPECT/CT, we found that radiolabeled autologous bone marrow-derived MSCs after intravenous administration distributed in the reticuloendothelial system and lung parenchyma, but accumulated unremarkably at the site of tSCI, whereas after intrathecal administration they spread rostraly in the cerebrospinal fluid and accumulated at the site of tSCI as early as 1 hour after administration, with increasing accumulation at 4 hours. The migration and homing potential of MSCs after intrathecal administration was maintained even one and a half years after tSCI. We observed no serious side effects during and after the procedure, however, neurologic recovery was minimal and could not be attributed solely to MSCs administration.Discussion: This case suggests that hybrid SPECT/CT imaging could be successfully used to track radiolabeled MSCs within the first day after intravenous and intrathecal administration of MSCs in a patient with tSCI without serious side effects.

The Use of Autologous Chondrocyte and Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects in Human Knee Joints-A Systematic Review and Meta-Analysis.

Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with significant functional and socioeconomic consequences. Implants consisting of autologous chondrocytes or mesenchymal stem cells (MSC) seeded onto scaffolds have been suggested as promising therapies to restore these defects. However, the degree of integration between the implant and native cartilage still requires optimization. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, CINAHL) to identify studies that used autologous chondrocyte implants (ACI) or MSC implant therapies to repair chondral defects of the tibiofemoral joint. Data on the integration of the implant-cartilage interface, as well as outcomes of clinical scoring systems, were extracted. Most eligible studies investigated the use of ACI only. Our meta-analysis showed that, across a total of 200 patients, 64% (95% CI (51%, 75%)) achieved complete integration with native cartilage. In addition, a pooled improvement in the mean MOCART integration score was observed during post-operative follow-up (standardized mean difference: 1.16; 95% CI (0.07, 2.24), p = 0.04). All studies showed an improvement in the clinical scores. The use of a collagen-based scaffold was associated with better integration and clinical outcomes. This review demonstrated that cell-seeded scaffolds can achieve good quality integration in most patients, which improves over time and is associated with clinical improvements. A greater number of studies comparing these techniques to traditional cartilage repair methods, with more inclusion of MSC-seeded scaffolds, should allow for a standardized approach to cartilage regeneration to develop.

The Clinical Use of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Secondary Alveolar Cleft

The Clinical Use of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Secondary Alveolar Cleft

Первые результаты применения стволовых клеток в лечении стрессового недержания мочи у женщин

Introduction. Stress urinary incontinence is a problem not only for the female, but is also a social, medical and economic issue for the community. The main method of treating stress urinary incontinence in women is surgical intervention with the use of synthetic mesh tape. Possibilities of intra and post-surgical complications is a major setback of surgical treatment. Attempts to restore/improve urethral sphincter functions by implanting stem cells has become a perspective method. Methods and materials. Ten female patients from the Urological Clinic of the Grodno State Medical University were chosen for treatment using autologous mesenchymal stem cells. All of them were undergone tourological and gynecological examinations. All chosen patients filled in an Incontinence Quality of Life questionnaire, related to the continention of urine before and after the implant of stem cells. After the explantation of fatty tissue, autologous mesenchymal stem cells were extracted and cultivated, a mixture of stem cells with a gelatine-based substance. Stem cells were introduced para-urethrally and into the urethral wall. Results. After 12 months after the implant 9 women completely retained urine during physical activity. No imperative disorders noted. One patient continued losing urine during physical activity, and her condition remained without improvement. Conclusion. A positive result by criteria of urine retention, urination disorder, and a subjective evaluation of quality of life was achieved in 90% of patients. A lack of even a small positive effect on one patient gives evidence to pathological changes in the organs of the genitourinary, in which stem cell therapy has a low effectiveness. First results inspire a careful optimism, but a continuation of research is required due to a small number of observations.

Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial.

Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants. In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively. Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×109±2.2×109 to 1.3×1010±1.7×1010 EVs/mL) within 24 hours after injection of MSCs (P=0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV numberLog [95% CI, 1.144-28.589]; P=0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively (P<0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy (P=0.0479). In contrast, trophic factor levels were not changed after MSC therapy. This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity. URL: https://www. gov; Unique identifier: NCT01716481.

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.

Remarkable pain control and functional improvement in clubfeet-related ankle osteoarthritis post autologous expanded mesenchymal stem cell therapy

Ankle joint osteoarthritis (OA) is not as common as knee and hip OA but it causes a significant socioeconomic burden in society. The causes of ankle OA could be primary or secondary to previous ankle trauma, inflammatory arthritis like rheumatoid arthritis, avascular necrosis, post-infectious, clubfoot, and other rare causes. Ankle OA is hard to treat conservatively. Limited options, including physiotherapy, supportive custom-made braces, weight reduction, and anti-inflammatory medicines. Standard surgical options are joint arthrodesis and ankle replacement. Arthrodesis can limit the movement of talar and subtalar joints, making it difficult to be accepted by athletes who require functional joint movement. Ankle replacement might last between five and ten years and is sometimes technically challenging. Herein we report a case of a seventy-one-year-old male property investor. His past medical history of bilateral congenital clubfeet with the left foot more affected and pointed backward required three surgeries at the age of two through five to align the foot in the correct direction, and his left ankle was fused. In his mid-forties, he had mild ankles discomfort which was managed by suitable orthotics, despite the ankle pathology he enjoys various recreational physical sports at a premium competitive level with determination. At the age of sixty-seven, his symptoms increased gradually. He was diagnosed with severe secondary severe subtalar and mild talar OA, confirmed by X-rays; by the age of seventy-one, he had significant pain and loss of ankle function to the extent he could hardly walk five steps or play any sport. He failed conservative management with various supportive orthotics and long-term anti-inflammatory medicines. He elected experimental autologous fat-derived expanded mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP). After two doses nine months apart, he responded superbly to become pain-free. Three months after the second dose, he was able to walk normally, play sports, and intend to return to competitive table tennis, but we recommended continuing using supportive orthotics. We predict MSCs slow the progression of OA. We believe this is the future medicine to try efficiently and safely regardless of the number of booster doses given.

Influence of exposure to microbial ligands, immunosuppressive drugs and chronic kidney disease on endogenous immunomodulatory gene expression in feline adipose-derived mesenchymal stem cells.

Feline autologous mesenchymal stem cells (MSCs) show promise for immunomodulatory activity, but the functional impact of chronic kidney disease (CKD), concurrent immunosuppressive drug administration or infection is unknown. The study objectives compare endogenous cytokine gene expression (interleukin [IL]-6, IL-10, IL-12p40, IL-18 and transforming growth factor beta [TGF-β]) in adipose-derived MSCs (aMSCs) from cats with and without CKD, following in vitro exposure to microbial ligands and treatment with common immunosuppressive drugs. Previously obtained aMSCs, phenotype CD44+, CD90+, CD105+ and MHCII-, from cats with (n = 6) and without (n = 6) CKD were compared via real-time PCR (RT-PCR) for immunomodulatory gene expression. aMSCs were exposed in vitro to lipopolysaccharide (LPS), peptidoglycan or polyinosinic:polycytidylic acid (Poly I:C), simulating bacterial or viral exposure, respectively. aMSCs were also exposed to ciclosporin, dexamethasone or methotrexate. Gene expression was measured using RT-PCR, and Cq was utilized after each run to calculate the delta cycle threshold. aMSCs isolated from healthy and CKD cats showed no significant differences in gene expression in the five measured cytokines. No significant changes in measured gene expression after drug treatment or microbial ligand stimulation were observed between normal or CKD affected cats. Proinflammatory genes (IL-6, IL-12p40 and IL-18) showed altered expression in aMSCs from both groups when compared with the same cells in standard culture after exposure to methotrexate. Poly I:C altered IL-6 and TGF-β gene expression in aMSCs from both healthy and CKD cats when compared with the same cells in standard culture. The five genes tested showed no statistical differences between aMSCs from healthy or CKD cats. There was altered cytokine gene expression between the control and treatment groups of both healthy and CKD cats suggesting feline aMSCs have altered function with immunosuppressive treatment or microbial ligand exposure. Although the current clinical relevance of this pilot study comparing brief exposure to select agents in vitro in aMSCs from a small number of cats is unknown, the study highlights a need for continued investigation into the effects of disease and concurrent therapies on use of cell-based therapies in feline patients.

Intravenous Transplantation of Human Hair Follicle-Derived Mesenchymal Stem Cells Ameliorates Trabecular Bone Loss in Osteoporotic Mice.

Background: Hair follicles harbor a rich autologous stem cell pool and human hair follicle-derived mesenchymal stem cells (hHF-MSCs) have multi-lineage differentiation potential. Many sources of MSCs include hHF-MSCs have been attractive candidates for cell therapy, regenerative medicine and tissue engineering. The present study is to explore the effect of intravenous transplantation of hHF-MSCs on bone mass in osteoporotic mice and its mechanism, and provides prospects for clinical applications for the treatment of osteoporosis with hHF-MSCs. Methods: Physically pull out about 20 hairs with intact hair follicles from the occipital area of the scalp of healthy volunteers, and extract hair follicle-derived fibroblast-like cells. These cells were cultured and characterized in vitro. Intravenous injection of hHF-MSCs was performed on ovariectomy-induced and age-related osteoporotic SCID mice for osteoporosis treatment. The mice were sacrificed 7 weeks after the second injection and samples were collected. The long bones and L1 vertebrae were collected for micro-CT scan, histomorphometry and immunohistochemical analysis. Peripheral serum were collected for ELISA analysis and antibody array. Results: Hair follicle-derived fibroblast-like cells were defined as hHF-MSCs. Intravenous transplantation of hHF-MSCs can better restores trabecular bone mass in osteoporotic mice. The double calcein labeling assay, trap staining of bones and ELISA analysis in peripheral serum showed enhanced bone formation and weakened bone resorption after transplantation. Antibody array and immunohistochemical analysis showed that several cytokines including OPG, Wnt2b, Noggin, VCAM-1 and RANKL might be involved in this process. Conclusion: Human HF-MSCs transplantation can combat trabecular bone loss induced by menopause and aging in mice. And the above mechanism that hHF-MSCs transplantation inhibits bone resorption and promote bone formation is related to OPG, Wnt2b, VCAM-1, Noggin and RANKL.