Autologous Mesenchymal Stem Cells Research Articles

Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence

Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence

FRAGMENTED THIGH INJURY: TREATMENT WITH PREBIOTICS, NANOPARTICLES, AND CELL THERAPY

The purpose of this study was to investigate the possibility of staged local treatment of an infected mine-explosive wound using a gel containing Bacillus spp., cerium oxide nanoparticles, and cell therapy. Object and Methods. The article presents a clinical case demonstrating the effective staged treatment of a 57-year-old patient with a fragmentary fracture of the right femur and a large purulent wound of the right thigh. The patient underwent Ex-fix rod-type femur-tibia stabilization and resection of a post-traumatic aneurysm of the right superficial femoral artery. In the first stage of treatment, two sessions of negative pressure wound therapy (NPWT) were applied, with pressures ranging from 75-115 mm Hg and a session duration of 4-5 days. In the second stage, local treatment involved a combination of antiseptics and probiotics (Bacillus spp.) alongside cerium oxide nanoparticles. By the 7th day, the eradication of pathogenic microflora was achieved, allowing for the third stage of treatment—application of autologous mesenchymal stem cells. Results: The treatment of combat trauma has become increasingly relevant in Ukraine and globally due to its complexity and the rising proportion of multiple and combined injuries, which account for 25-60% of cases. Infectious complications occur in 25% of combat trauma cases and are responsible for 70% of related deaths. Most structural and functional disorders associated with wound infections develop at the time of injury, intensify over time, and require immediate surgical intervention, improvements in local treatment methods, and new approaches for wound closure. Conclusions: The use of a combination of probiotics and NPWT therapy led to a rapid reduction of the inflammatory process. Clinical observations showed accelerated wound cleansing from fibrin and necrotic tissue. The combined treatment significantly reduced the size and depth of wound due to the formation of active pink granulation tissue (observed by days 8-9) and marginal epithelialization by days 10-13. During this period, no pathogenic flora were detected, allowing for the subsequent application of autologous mesenchymal stem cells. This treatment approach reduced the need for antibacterial drugs and prevented the need for additional surgical interventions. The inclusion of cerium oxide nanoparticles was an effective enhancement for cell transplantation, facilitating stem cell delivery and contributing to the treatment of large wounds.

Shock wave-pretreated ADMSCs of cell-sheet scaffold (CSS) patched on left ventricular wall (LVW) inhibited LVW remodeling in mini-pig MI ---role CSS on counteracting Laplace's Law of LVW stress: Experimental study.

We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI). Mini-pigs (n=20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×107 in CSS on LV myocardium), and group 4 [old MI + SW (0.12mJ/mm2 for total 140 shots)-pretreated ADMSCs in CSS on LV myocardium]. Treatments started on day 28 after MI induction. In vivo and in vitro studies were conducted. Cell viability/relative mitochondria DNA expression/mitochondrial cytochrome C/adenosine triphosphate concentration in ADMCSs and protein expressions of angiogenesis factors (vascular endothelial growth factor [VEGF]/stromal cell-derived factor-1 [SDF-1])/mitochondrial respiratory chain complexes I-IV/oxygen consumption rate were higher in group 4 than in group 3 (P<0.001). By day 180, LVEF and small vessel numbers in the peri-infarct or infarct area were highest in group 1, lowest in group 2, and significantly lower in group 3 than in group 4. In contrast, the LV dimension was opposite to the pattern of change in LVEF in all groups (P<0.0001). The basal/middle/apical infarct and fibrotic areas were inversely related to LVEF in all groups (all P<0.0001). Protein levels of angiogenetic markers (SDF-1α/C-X-C chemokine receptor type 4/VEGF/angiopoietin-1) were significantly and persistently increased from groups 1 to 4. In contrast, protein levels of endothelial-cell markers (von Willebrand factor or endothelial nitric oxide synthase) showed an identical pattern to LVEF in all groups (all P<0.0001). SW pretreatment of ADMSCs seeded in CSS offered significant benefits in preserving LV performance and ameliorating LV remodeling in mini-pigs with old MI.

Translational horizons in stem cell therapy for osteonecrosis of the femoral head: a journey from basic research to clinical practice through bibliometric insights

BackgroundOsteonecrosis of the femoral head (ONFH) significantly impacts young and middle-aged adults, with steroid use implicated in many cases. Traditional treatments have limited efficacy, prompting a shift towards innovative approaches, such as stem cell therapy, offering less invasive regenerative solutions.MethodsUsing bibliometric analysis from 1997 to 2023, we identified 392 articles on stem cell therapy for ONFH from the Web of Science Core Collection and analysed them using VOSviewer and CiteSpace to identify key trends and research directions.ResultsFrom 1997 to 2023, stem cell therapy for ONFH research expanded significantly, with 392 articles evidencing global collaboration, particularly from China, the United States and South Korea. The field is characterised by 158 core authors across 26 clusters and contributions from 417 institutions in 104 research clusters, with Shanghai Jiao Tong University as a notable leader. This research is disseminated through 23 journal clusters, emphasising interdisciplinary work, with Clinical Orthopaedics and Related Research among the most influential journals. Key findings include the identification of the most influential papers, highlighting advances, such as use of autologous mesenchymal stem cells (MSCs) and innovative delivery mechanisms. High-frequency keyword analysis further mapped the evolution of the field, from basic mechanisms to advanced therapies, underscoring a trend towards more targeted stem cell treatments for ONFH.ConclusionStem cell therapy for ONFH has advanced significantly, showcasing a successful transition from basic research to clinical practice, particularly highlighted by developments in use of autologous MSCs and delivery methods. Future research will focus on refining therapies through exosome technology, targeted modulation of stress and inflammation and integration with surgical techniques, with the aim of tailored patient care and improved ONFH outcomes.

Gingival mesenchymal stem cells derived from patients with rheumatoid arthritis treat experimental arthritis

AbstractA therapeutic strategy using mesenchymal stem cells (MSCs) has been accepted as a novel therapy for treating rheumatoid arthritis (RA). Human gingiva‐derived MSCs (GMSCs) are superior in regulating immune responses. Autologous MSCs are the optimal candidate to avoid the potential risks of allogenic MSCs. However, whether autologous GMSCs from RA patients are therapeutic remains unknown. In this study, we compared the therapeutic efficacy of GMSCs derived from patients with RA (RA‐GMSCs) and that from health donors (H‐GMSCs) in vivo and in vitro. Then, we utilized RNA‐sequencing, the molecular and cellular assays to determine the immunomodulatory molecules that contribute to the therapeutic effect of RA‐GMSCs on both collagen‐induced arthritis (CIA) and humanized synovitis models. We demonstrated that GMSCs derived from patients with RA (RA‐GMSCs) and health donors (H‐GMSCs) shared a similar expression of immunomodulatory molecules. Moreover, RA‐GMSCs were as effective as H‐GMSCs in suppressing T‐cell proliferation, proinflammatory cytokines secretion, as well as osteoclast differentiation in vitro. In addition, RA‐GMSCs had a robust therapeutic effect on the CIA model. Importantly, RA GMSCs can survive for at least 24 days in a CIA mouse model and can be distributed in the spleen, lymph nodes, and joints. Specifically, RA‐GMSCs decreased the frequency of Th1 and Th17 cells whereas enhanced Treg cells, reducing the joint histopathological scores of lymphocytes, osteoclasts, and cartilages. Moreover, RA‐GMSCs were also effective in suppressing inflamed synoviocyte proliferation, migration, and invasion in vitro, and cartilage invasion in a humanized synovitis model in vivo. Our study implies that manipulation of RA‐GMSCs is therapeutic in CIA mice and humanized synovitis models and may have therapeutic potential in RA patients using autologous GMSCs in the future.

Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

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

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

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 therapy with autologous mesenchymal stem cells for premature baby with neonatal sepsis and bronchopulmonary dysplasia: Case report

Cell therapy with autologous mesenchymal stem cells for premature baby with neonatal sepsis and bronchopulmonary dysplasia: Case report

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.

Efficacy of mesenchymal stem cell transplantation on major adverse cardiovascular events and cardiac function indices in patients with chronic heart failure: a meta-analysis of randomized controlled trials

BackgroundThe effects of mesenchymal stem cells (MSCs) on heart failure (HF) have been controversial. This study was conducted to investigate whether the transplantation of MSCs after HF could help improve clinical outcomes and myocardial performance indices.MethodsUsing a systematic approach, electronic databases were searched for randomized controlled trials (RCTs), which evaluated the transplantation of MSCs after HF. The outcomes owf interest included clinical outcomes and myocardial function indices. We also assessed the role of age, cause of heart failure, cell origin, cell number, type of donor (autologous/allogeneic), and route of cell delivery on these outcomes. Using the random-effects method, a relative risk (RR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) were pooled.ResultsSeventeen RCTs including 1684 patients (927 and 757 patients in the intervention and control arms, respectively) were enrolled. The RR (95% CI) of mortality was 0.78 (0.62; 0.99, p = 0.04) in the MSC group compared to the controls. HF rehospitalization decreased in the MSC group (RR = 0.85 (0.71–1.01), p = 0.06), but this was only significant in those who received autologous MSCs (RR = 0.67 (0.49; 0.90), p = 0.008). LVEF was significantly increased among those who received MSC (MD = 3.38 (1.89; 4.87), p < 0.001). LVESV (MD = −9.14 (−13.25; −5.03), p < 0.001), LVEDV (MD = −8.34 −13.41; −3.27), p < 0.001), and scar size (standardized MD = -0.32 (-0.60; -0.05), p = 0.02) were significantly decreased. NYHA class (MD = −0.19 (−0.34; −0.06), p = 0.006), BNP level (standardized MD = −0.28 (−0.50; −0.06), p = 0.01), and MLHFQ (MD = −11.55 (−16.77; −6.33), p = 0.005) significantly decreased and 6-min walk test significantly improved (MD = 36.86 (11.22; 62.50), p = 0.001) in the MSC group. Trials were not affected by the participants’ etiology of heart failure, while trials with the autologous source of cells, MSC doses lower than 100 million cells, and intracoronary injection performed significantly better in some of the outcomes.ConclusionTransplantation of MSCs for ischemic or dilated heart failure patients may reduce all-cause mortality and improve clinical condition. Moreover, this treatment would improve left ventricular function indices and reduce scar size.Graphical

Industry affiliation does not predict outcomes of randomized controlled trials for mesenchymal stem cells in knee osteoarthritis

BackgroundThis research aims to determine the influence of industry on the outcomes of randomized controlled trials (RCTs) for Mesenchymal Stem Cell (MSC) treatments in knee osteoarthritis (OA). MethodsPubMed, Scopus, and Web of Science were searched from 2010 onwards using the terms “knee osteoarthritis” and “mesenchymal stem cells”. After identifying relevant RCTs, studies were categorized as industry-affiliated or non-industry-affiliated. They were also classified as favorable if they achieved statistically significant (p < 0.05) results with MSC injections compared to control. Chi-squared tests were employed to analyze the relationship between industry affiliation and study outcome. ResultsPost exclusion criteria, 38 studies were analyzed. Of these, there were 20 (52.6%) industry affiliated (IA) and 18 (47.4%) non-industry affiliated (NIA) studies. Among the 20 IA studies, 17 (85.0%) reported favorable outcomes for MSC treatment arm, with the remaining 3 (15.0%) showing analogous (no difference between treatment arms) results. For the 18 NIA studies, 15 (83.3%) were favorable, and 3 (16.6%) were analogous. No significant difference in outcomes was observed between IA and NIA studies (p = 0.888). Analysis of patient reported outcomes also revealed no significant difference. Of note, studies using allogeneic MSCs were more likely to be IA than studies using autologous MSCs (p = 0.005) ConclusionThis study demonstrated no strong association between industry affiliation and the outcomes of RCTs for MSC treatments in knee OA. Despite this, the potential influence of industry ties should always be considered when applying study findings to new treatment modalities for patient care.

Proteomic profiling of regenerated urinary bladder tissue in a non-human primate augmentation model

Urinary bladder dysfunction can be caused by environmental, genetic, and developmental insults. Depending upon insult severity, the bladder may lose its ability to maintain volumetric capacity and intravesical pressure resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is utilized to increase bladder capacity to preserve renal function using autologous bowel tissue as a “patch.” To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) co-seeded with CD34+ hematopoietic stem/progenitor cells (HSPCs) onto a pliable synthetic scaffold [poly(1,8-octamethylene-citrate-co-octanol)(POCO)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in our baboon bladder augmentation model. We set out to determine the global protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogeneous protein expression between the tissues following long-term engraftment. We posit that stem cell-seeded scaffolds can recapitulate tissue that is nearly indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.

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

Injectable porous microspheres for articular cartilage regeneration through in situ stem cell recruitment and macrophage polarization

In situ mesenchymal stem cells (MSCs) regenerative therapy holds promising potential for treating osteoarthritis. However, MSCs engraftment and intra-articular inflammation limit the therapeutic efficacy of this approach. This study introduces porous microspheres (PMs) composed of aldehyde-modified poly(lactic-co-glycolic acid), that encapsulate platelet derived growth factor-AB and kartogenin. Metformin (Met) is also incorporated onto the microsphere through a Schiff base reaction to create PMs@Met. In vitro, in vivo and ex experiments revealed that PMs@Met can be injected into the joint cavity, effectively recruiting endogenous MSCs in situ. This approach creates a favorable environment for MSCs proliferation. It also controls the intra-articular inflammatory environment by modulating the polarization of synovial macrophages, ultimately promoting cartilage repair. In summary, our study presents an innovative tissue engineering strategy for the treatment of osteoarthritis-induced articular cartilage injuries. Statement of significanceCell therapy using autologous mesenchymal stem cells (MSCs) has potential to slow the progression of osteoarthritis (OA). Nonetheless, there are some disadvantages to adopting in situ MSCs therapy, including difficulties with MSC engraftment into cartilage-deficient regions, the effect of intra-articular inflammation on MSC therapeutic efficacy, and attaining selective chondrogenic MSC differentiation. We created injectable PLGA microspheres (PMs) that were loaded with PDGF-AB and KGN. Metformin was bonded to the surface of microspheres using a Schiff base reaction. The microspheres can recruit intra-articular MSCs and encourage their development into chondrocytes. The microspheres actively modulate the inflammatory joint environment by altering synovial macrophage polarization, thereby supporting MSCs in effective cartilage treatment. To summarize, microspheres hold great potential in the treatment of OA.

Seven-Year Longitudinal Study: Clinical Evaluation of Knee Osteoarthritic Patients Treated with Mesenchymal Stem Cells.

Background/Objectives: Numerous studies have demonstrated the safety and efficacy of intraarticular stem cell injections for treating osteoarthritic knee joints, reporting symptom reduction and pain relief within a few months of treatment. Here, we report the results of a 7-year follow-up after a single intraarticular injection of 0.5-1 × 107 autologous adipose tissue-derived mesenchymal stem cells in patients with OA (Kellgren-Lawrence grade 2 to 4). Methods: Nine patients were treated, and two patients had bilateral disease. Patients were evaluated clinically and radiologically using X-ray and MRI. A comprehensive statistical analysis was undertaken to evaluate the obtained results. Results: All clinical scores and range of motion significantly improved within the first six months after injection. At the 18-month time point, a significant improvement in cartilage structure was observed on MRI while X-ray showed no changes in subchondral bone of distal femur and proximal tibia. At the 60-month time point, the clinical scores were still improved compared to baseline, except for the range of motion, which decreased almost back to the baseline level. At 84 months, the clinical scores decreased significantly toward the baseline level, but the MRI structural characteristics of cartilage still remained significantly better than those measured at baseline. Conclusions: Adipose tissue-derived stem cell therapy has substantial long-term clinical effects on patients with knee osteoarthritis.

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.

Cell-based medicinal products: a review of current research

INTRODUCTION. Cell therapies and tissue-engineered products are aimed at patients with severe conditions (genetic and neurodegenerative disorders, cancers, musculoskeletal injuries, burns, etc.) that lack alternative treatment options. Analysis of clinical efficacy data on cellbased medicinal products is important for understanding their translational potential in personalised medicine.AIM. This study aimed to review key trends in cell therapy, analyse data on approved cell therapies and tissue-engineered products, and assess challenges and prospects for their use.DISCUSSION. This article analyses data on the composition of cell therapies and tissue-engineered products, indications for their use, and the results of clinical studies. Cell-based medicinal products are derived from autologous or allogeneic mesenchymal and limbal stem cells, epithelial cells, chondrocytes, native or genetically engineered haematopoietic stem cells, genetically engineered lymphocytes (CAR-T, CAR-NK), etc. Medicinal products based on cell technologies have been approved in many countries, including the USA (approximately 30), the European Union (approximately 20), Japan (18), South Korea (15), etc. As of today, two cell therapies have been granted marketing authorisation in the Russian Federation. The first is based on CAR-T cells (a gene therapy product), and the other is based on chondrocytes (a cell-based medicinal product); the latter has been developed in Russia. The main advantages of cell therapy products include higher efficacy and fewer adverse drug reactions in comparison with standard treatment modalities. The main challenges of cell therapy include the risks of immune reactions and mutagenesis associated with lentiviral vectors or CRISPR/Cas9 technology, as well as limited efficacy of CAR-T and CAR-NK cells due to immunosuppressive properties of tumour microenvironment.CONCLUSIONS. In comparison with conventional treatment approaches, the use of cell therapies and tissue-engineered products can help effectively eliminate defects in various body tissues, avoid highly invasive surgical interventions, and reduce regeneration time. Thus, ensuring development of similar but at the same time more affordable Russian medicinal products can bring great benefits for the healthcare system of the Russian Federation.

Activated allograft combined with induced membrane technique for the reconstruction of infected segmental bone defects

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4–17) cm in length. After a mean follow-up of 71.84 (61–82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5–28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.

System proteinase/inhibitors in the pathogenesis of experimental kidney tuberculosis

BACKGROUND: Damage to the kidney parenchyma of various origins is associated with the accumulation of extracellular matrix proteins, the regulation of which involves the matrix metalloproteinase/inhibitor system. AIM: To evaluate the pathogenetic role of the proteinase/blood inhibitor system in experimental renal tuberculosis. MATERIAL AND METHODS: When modeling the process, a clinical strain 5582 of the Beijing genotype with multidrug resistance of mycobacteria was used. The study was conducted on 20 rabbits, divided into three groups: the first (n=6) included infected untreated animals; in the second (n=7) and third (n=7) anti-tuberculosis therapy was administered orally for 18.5 weeks; in the third, treatment was carried out in combination with a single injection of autologous mesenchymal stem cells into the ear vein. Blood levels of matrix metalloproteinases-1 and -9, tissue inhibitor of metalloproteinases-1, cystatin C and neutrophil elastase were determined. Morphological changes in the kidney parenchyma at the end of the experiment were assessed using 26 indicators, including tubulointerstitial and vascular changes. The median and interquartile ranges were calculated, the Kruskal–Wallis test, analysis of covariance, and the projective classification method were used. RESULTS: The progression of kidney tuberculosis was accompanied by a significant increase in the level of neutrophil elastase by 1.9 times, matrix metalloproteinase-9 by 2.2 times, and cystatin C by 1.5 times compared to the initial level. The treatment carried out in the second and third groups contributed to the normalization of these indicators. The concentrations of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in all three groups did not change relative to the baseline level. Covariance analysis showed that in the pathogenesis of renal tuberculosis changes in matrix metalloproteinase-1 (p=0.003), matrix metalloproteinase-9 (p=0.002), tissue inhibitor of metalloproteinases-1 (p=0.01) and cystatin C (p=0.0001) were primarily associated with vascular changes, found in all study groups. A linear combination containing three morphological characteristics allowed us to identify differences between the three groups with 90% accuracy. CONCLUSION: Renal tuberculosis, caused by a multidrug-resistant pathogen, is characterized by an imbalance in the proteinase/inhibitor system and impaired renal function, the degree of which is associated with the morphological characteristics of vascular and tubulointerstitial changes.