Injection Of Stem Cells Research Articles

Global research status and hot trends in stem cells therapy for Intervertebral disc degeneration: A bibliometric and clinical study analysis.

Background: Stem cells (SCs) therapy for intervertebral disc degeneration (IDD) has been studied for nearly 20 years and it is an important part of regenerative medicine and tissue engineering research, as well as a current research hotspot and challenge. Although the volume of literature has shown an annual growth trend, there is no literature available for bibliometric and clinical analysis of the content of multiple databases in this field. Methods: The articles were obtained from the WOSCC, Scopus, Pubmed, and ClinicalTrials on 27 December 2021. Three scientometric software (VOSviewer 1.6.17, CiteSpace 5.8.R.1 and Scimago Graphica) were used to perform bibliometric and knowledge-map analysis. Results: We included 867 articles from WOSCC, 716 articles from Scopus and 6 clinical studies from ClinicalTrials for literature analysis. Our results showed that China was the country with the highest number of publications, with the United States (US) being the leader in terms of international collaborations and the number of citations. Sakai D, Grad S and Hoyland JA had made outstanding contributions for their high productivity and the quality articles. Spine was the most published and most cited journal, in addition to Spine Journal and Biomaterials, which were also more authoritative journals and had received high citations. All of them had received high citations. Keyword co-occurrence studies suggested that the current hotspots were in mechanistic studies, including inflammation, apoptosis, exosome, autophagy, and others. Some studies had also investigated tissue-engineered scaffolds of SCs to better repair degenerated discs. Clinical studies were relatively scarce. Direct injection of Mesenchymal Stem Cells (MSCs) into degenerated discs for the treatment of Degenerative disc disease (DDD) was the current direction of research. Conclusion: This study demonstrates the global research hotspots, trends and clinical use of SCs in the treatment of IDD. It can help scholars to quickly understand the current status and hotspots of research in this field, and also provide some guidance and reference for those who are currently researching in this area.

Exclusive generation of rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells.

SummaryBlastocyst complementation denotes a technique that aims to generate organs, tissues, or cell types in animal chimeras via injection of pluripotent stem cells (PSCs) into genetically compromised blastocyst-stage embryos. Here, we report on successful complementation of the male germline in adult chimeras following injection of mouse or rat PSCs into mouse blastocysts carrying a mutation in Tsc22d3, an essential gene for spermatozoa production. Injection of mouse PSCs into Tsc22d3-Knockout (KO) blastocysts gave rise to intraspecies chimeras exclusively embodying PSC-derived functional spermatozoa. In addition, injection of rat embryonic stem cells (rESCs) into Tsc22d3-KO embryos produced interspecies mouse-rat chimeras solely harboring rat spermatids and spermatozoa capable of fertilizing oocytes. Furthermore, using single-cell RNA sequencing, we deconstructed rat spermatogenesis occurring in a mouse-rat chimera testis. Collectively, this study details a method for exclusive xenogeneic germ cell production in vivo, with implications that may extend to rat transgenesis, or endangered animal species conservation efforts.

Intravenous Injection of SDF-1α-overexpressing Bone Marrow Mesenchymal Stem Cells has a Potential Protective Effect on Myocardial Ischemia in Mice.

Neutrophils are involved in the injury of myocytes during myocardial ischemia (MI). Stem cells migrate to the site of myocardial injury under homing signals and play a protective role, such as inhibiting inflammation. Chemokine SDF-1α and its related receptor CXCR4 are upregulated after myocardial infarction, which may play an important role in stem cell homing. This study aimed to explore the potential therapeutic effect of SDF-1α-modified bone marrow mesenchymal stem cells on myocardial ischemia/reperfusion (I/R) injury. We explored the role of SDF-1α modified bone marrow mesenchymal stem cells in vivo and in vitro. SDF-1α and CXCR4 expression was detected under hypoxia/reoxygenation (H/R) condition. Cell migration was detected by the transwell method. The levels of SDF-1α and IL-1β, IL-6, IL-10, and TNF-α were detected in different groups. In vitro, SDF-1α was mainly upregulated and secreted by cardiomyocytes, and cardiomyocytes recruited stem cells through the SDF-1/CXCR4 pathway to reduce the damage of polymorphic mononuclear neutrophils to cardiomyocytes under H/R. Upregulation of SDF-1α increased the migration ability of BMSC Stem Cells to H/R-induced cardiomyocytes. In vivo, intravenous injection of SDF-1α genemodified BMSC Stem Cells reduced inflammatory infiltration in the injured area as well as the level of systemic inflammatory factors. SDF-1α-overexpressing BMSC Stem Cells protected the heart function of mice and significantly reduced I/R-induced myocardial injury, which has a potential protective effect on MI.

Co-overexpression of VEGF and Smad7 improved the therapeutic effects of adipose-derived stem cells on neurogenic erectile dysfunction in the rat model.

Cavernous nerve injury is the main cause of erectile dysfunction (ED) after radical prostatectomy (RP). In our previous study, injection of adipose-derived stem cells (ADSCs) into the cavernosum can repair damaged cavernosum nerves and ED can be restored to a certain extent. In order to improve these therapeutic effects, we evaluated the efficacy of ADSCs co-modified with VEGF and Smad7 in a rat model. SD rats were randomly divided into six groups: a sham surgery group, and the five bilateral cavernous nerve injury (BCNI) groups were injected with ADSC or ADSCs genetically modified by VEGF (ADSC-V), Smad7 (ADSC-S), or VEGF&Smad7 (ADSC-V&S) or phosphate-buffered saline (PBS). The results indicated that the erectile function of the ADSC-V, ADSC-S, and ADSC-V&S groups was significantly recovered, and the erectile function of the ADSC-V&S group was more distinctly recovered as compared to the other groups. The same results are shown in the expression of neuronal nitric oxide synthase and the smooth muscle/collagen ratio of penile tissue comparing the ADSC-V&S group to the ADSC-V and ADSC-S group. These experimental data suggest that ADSCs co-overexpressed with VEGF and Smad7 can significantly improve erectile function after BCNI. This study provides new therapeutic thoughts for ED following RP.

Biomimicking nanofibrous gelatin microspheres recreating the stem cell niche for their ex-vivo expansion and in-vivo like differentiation for injectable stem cell transplantation.

Stem cells based novel treatment modality for degenerative and immune dysfunction diseases created a huge demand of suitable carriers to support ex-vivo production of quality stem cells, and effective in-vivo transplantation of stem cells and their fate. In spite of promising candidature of nanofibrous microspheres (NFM) to recreate native stem cell niches to be used for possible scaling-up for ex-vivo stem cells expansion, it remains fairly unexplored. A systematic study on the stem cell-NFM interaction comparative with commercial microspheres (CM) has been performed for the first time. Gelatin NFM with variable physicochemical properties such as size, surface properties, surface chemistry, and variable degradability were prepared using microemulsion coupled with thermally induced phase separation (TIPS) method. Effect of physicochemical properties of NFM and their cellular interaction such as binding, morphology, metabolic activity and proliferation studies were performed using human bone marrow-derived mesenchymal stem cells (hBMSCs), human dental follicle stem cells (hDFSCs) and human gingival fibroblast (HGF) cells and compared with the commercial and solid microspheres. Gelatin NFM supports excellent cell binding, proliferation, metabolic activities and chemical cues specific differentiation. All out-turns indicate that NFM stand to be an outstanding candidate for ex-vivo cells' expansion and injectable carriers for stem cell transplantation.

Intratunical injection of rat-derived bone marrow mesenchymal stem cells prevents fibrosis and is associated with increased Smad7 expression in a rat model of Peyronie’s disease

ObjectivePeyronie’s disease (PD) is a fibrotic disorder of the penis, but effective treatments are lacking. Here, we observed the effects of rat-derived bone marrow mesenchymal stem cells (BMSCs) injection in the active phase and chronic phase in a rat model of PD, and the possible mechanism was analysed with fibroblasts derived from rat penile tunica albuginea (TA).MethodsThirty-two male Sprague-Dawley rats were divided into four groups. In sham group, the rats were injected with 50 µL of vehicle. In the PD group, the rats were injected with 50 µg TGF-β1. In the PD + BMSCs early treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 1 day. In the PD + BMSCs late treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 106 BMSCs after 28 days. Twenty-seven days after the last injection, the erectile function of the rats was measured, and then, penile fibrosis was analysed by histology and western blot. In vitro, fibroblasts derived from rat penile TA were used to identify a possible antifibrotic mechanism of BMSCs, and a Smad7 expression vector was used as a positive control. Fibroblasts were pretreated with the Smad7 expression vector or BMSCs for 48 h and then activated with 10 ng/mL TGF-β1 for 24 h. Cells viability was assessed, and Smad7, collagen 3, elastase-2B and osteopontin expression levels were analysed by immunofluorescence and western blot. Furthermore, fibroblasts were transfected with Smad7 siRNA or scramble control to observe whether the effects of BMSCs could be offset.ResultsErectile function obviously improved, and fibrosis of penile TA was prevented after BMSCs treatment compared with that in the rats with PD. Furthermore, the effects of BMSCs treatment in the active phase were better than those in the chronic phase. After cocultured with BMSCs, cell viability was not affected, Smad7 expression was upregulated, and collagen 3, elastase-2B and osteopontin levels were decreased in the TGF-β1-treated fibroblasts. After transfection with Smad7 siRNA, the antifibrotic effects of BMSCs were offset.ConclusionsThe antifibrotic effects of BMSCs treatment in the active phase of the PD rat model were better than those in the chronic phase. A possible mechanism of BMSCs treatment was related to increased Smad7 expression, suggesting a possible effective and safe procedure for the treatment of PD.

Regeneration of artificial injuries external ear elastic cartilage of rabbits after stem cells local injection

Introduction: Every year, a large number of patients from developed countries turn to surgical departments with the reconstruction problems of the auricle cartilage. A some of surgical procedures was developed to correct minor defects due to the low regenerative capacity of elastic cartilage. Stem cells can potentially differentiate into chondroblasts and chondrocytes and restore cartilage integrity. Many factors influence on the differentiation and proliferation of stem cells, which complicates the method application. Therefore, the investigation of using stem cells to regeneration elastic cartilage is relevant. Aim: clarification the regeneration features of the artificial defect of the rabbits’ ear elastic cartilage after the stem cells injection. Materials and methods: The investigation was conducted on rabbits of chinchilla breed aged 1.5 months, weighing 2.5 kg. Artificial lesions measuring 2 x 7-10 mm were simulated on the cartilaginous plate of the outer ear with a scalpel. 0.5 ml of stem cell suspension (~5 million) obtained from the umbilical cord of rabbits by enzymatic method was injected into the defect site. Histological sections of the cartilage defect were prepared. The samples were stained by Weigert and Azure II methods. The relative density of collagen, elastin fibers, oxyphilic and basophilic tissue elements was programmatically evaluated. Results and discussion: The amount of fibers in the native elastic cartilage was more on 35% of the relative dermis. The newly formed tissues at the damage cartilage was like to the dermis after 2 months. Similar results were found on ear in 2.5 and 3 months after surgery. Native cartilage on histological sections almost was not oxyphilic. Maybe a significant number of acidic components was masked it. Dense connective tissue contains almost equal amounts of both components. Thus, it is possible to trace changes in the intercellular matrix that will characterize the direction of the regeneration process. The area of elastic cartilage defect was characterized by a significant presence of oxyphilic elements after 2 months of the stem cells addition. The ratio of oxyphilic and basophilic components in the native elastic cartilage was about to zero. For the dermis was 1.4-1.5. Dense scar connective tissue was characterized by a ratio about 1. Based on the results obtained, was assumed that the direction of stem cell proliferation is determined shortly after injection. Conclusion: The addition of stem cells to the area of the artificially created elastic cartilage defect of the rabbit's ear was not allow to obtain stable regenerative processes of cartilage tissue and the restoration of the intercellular matrix to its original state. The process of stem cell differentiation contributes the formation of dense connective tissue of the scar, which may be due to the presence of proinflammatory cytokines, growth factors and other biologically active molecules. This was not creating the necessary conditions for the cartilage regeneration.

Theory and Applications of the (Cardio) Genomic Fabric Approach to Post-Ischemic and Hypoxia-Induced Heart Failure.

The genomic fabric paradigm (GFP) characterizes the transcriptome topology by the transcripts’ abundances, the variability of the expression profile, and the inter-coordination of gene expressions in each pathophysiological condition. The expression variability analysis provides an indirect estimate of the cell capability to limit the stochastic fluctuations of the expression levels of key genes, while the expression coordination analysis determines the gene networks in functional pathways. This report illustrates the theoretical bases and the mathematical framework of the GFP with applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failures. GFP analyses revealed the myocardium priorities in keeping the expression of key genes within narrow intervals, determined the statistically significant gene interlinkages, and identified the gene master regulators in the mouse heart left ventricle under normal and ischemic conditions. We quantified the expression regulation, alteration of the expression control, and remodeling of the gene networks caused by the oxygen deprivation and determined the efficacy of the bone marrow mono-nuclear stem cell injections to restore the normal transcriptome. Through the comprehensive assessment of the transcriptome, GFP would pave the way towards the development of personalized gene therapy of cardiac diseases.

Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications.

For more than 20 years, researchers have isolated and identified postnatal dental pulp stem cells (DPSCs) from different teeth, including natal teeth, exfoliated deciduous teeth, healthy teeth, and diseased teeth. Their mesenchymal stem cell (MSC)-like immunophenotypic characteristics, high proliferation rate, potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs. In addition, several main application forms of DPSCs and their derivatives have been investigated, including stem cell injections, modified stem cells, stem cell sheets and stem cell spheroids. In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs. Therefore, DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration. In this review, we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine. We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions. The methodologies for therapeutic administration of DPSCs and their derivatives are introduced, including single injections and the transplantation of the cells with a support, as cell sheets, or as cell spheroids. We also summarize the underlying mechanisms of the regenerative potential of DPSCs.

Tissue-engineered tendon nano-constructs for repair of chronic rotator cuff tears in large animal models.

Chronic rotator cuff tears (RCTs) are one of the most common injuries of shoulder pain. Despite the recent advances in surgical techniques and improved clinical outcomes of arthroscopically repaired rotator cuffs (RCs), complete functional recovery-without retear-of the RC tendon through tendon-to-bone interface (TBI) regeneration remains a key clinical goal to be achieved. Inspired by the highly organized nanostructured extracellular matrix in RC tendon tissue, we propose herein a tissue-engineered tendon nano-construct (TNC) for RC tendon regeneration. When compared with two currently used strategies (i.e., transosseous sutures and stem cell injections), our nano-construct facilitated more significant healing of all parts of the TBI (i.e., tendon, fibrocartilages, and bone) in both rabbit and pig RCT models owing to its enhancements in cell proliferation and differentiation, protein expression, and growth factor secretion. Overall, our findings demonstrate the high potential of this transplantable tendon nano-construct for clinical repair of chronic RCTs.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

Human Adipose-Derived Stem Cells Delay Muscular Atrophy after Peripheral Nerve Injury in Rats.

Given that denervation atrophy often occurs in muscle after peripheral nerve injury, the effects of injections of human adipose-derived stem cells (hADSCs) and platelet-rich plasma (PRP) into muscle after peripheral nerve injury were examined. hADSCs were isolated from human subcutaneous fat tissue, and PRP was prepared from rat whole blood before injection into a rat sciatic nerve injury model. Muscle atrophy was evaluated by quantitating the gross musculature and muscle fiber area and walking footprint analysis. At 4 weeks post-surgery, there were significant differences in the sciatic functional index between experimental (injected with hADSCs, PRP, or combined hADSCs + PRP) and non-operated groups (p < 0.0001), but no significant differences were observed between the different treatment groups (p > 0.05). Post hoc Bonferroni tests also showed significant differences in the wet muscle weight ratios of hADSC, PRP, and combined groups compared to PBS group. The gastrocnemius muscle fiber area was larger in hADSC group and the combined group compared to PBS group at 4 weeks post-surgery. The injection of hADSCs delays muscular atrophy after sciatic nerve injury in rats; thus, hADSCs are a promising alternative for regenerating atrophied muscle.

Anti-Aging Effect of the Stromal Vascular Fraction/Adipose-Derived Stem Cells in a Mouse Model of Skin Aging Induced by UVB Irradiation.

Adipose-derived stem cells(ADSCs) have been used for anti-photo-aging. But the purification of ADSCs requires in vitro amplification and culture, there is considerable risk of direct treatment for patients. Stromal vascular fraction(SVF) is a biologically and clinically interesting heterogeneous cell population contains ADSCs. There are few reports on anti-aging effects of SVF in photo-aging skin. The present study investigated the anti-aging effect of stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) injection in photo-aging skin. The relationship between the dosage of injection and effect was also discussed. Thirty healthy, 6-week-old, nude rats were randomly divided into the control and experimental groups. The experimental group needing ultraviolet B (UVB) irradiation five days per week, and a duration of 8 weeks. According to different dose regimens of SVF and ADSCs, experiment rats were randomly grouped as the model control group, low-dose (LD) treatment group, middle-dose (MD) treatment group and high-dose (HD) treatment group. At 7 and 28 days post-treatment, specimens were harvested for histological and immunohistochemical analysis. We found that certain concentrations of cells (MD and HD groups) could improve the texture of photoaged skin. Changes in the epidermal cell layer were clearly observed after 7 days of treatment. The epidermal layer becomes thinner and more tender. After 28 days of treatment, the dermal tissue was thickened and the collagen content and proportion were improved. All these indicators showed no significant difference between the same dosages in the two treatment groups. Our results demonstrate that SVF may have anti-aging potential in photo-aging skin and the ADSCs play an important role in SVF. SVF maybe a potential agent for photo-anging skin and the most effective dose of SVF was 106 cells /100 µl/injection point. The proper injection interval may be 1.5 cm.

Gallic Acid Improves Therapeutic Effects of Mesenchymal Stem Cells Derived from Adipose Tissue in Acute Renal Injury Following Rhabdomyolysis Induced by Glycerol.

Acute kidney injury (AKI) is identified by a progressive reduction in the glomerular filtration rate (GFR) and retention of nitrogenous waste products. Traumatic and nontraumatic rhabdomyolysis is recently considered the main cause of AKI. According to several studies, stem cell treatment is a promising therapeutic strategy for many types of disorders including AKI. The main limitation of mesenchymal stem cells (MSCs) therapy is reducing cell survival in response to oxidative stress products in injured organ areas. Gallic acid (GA) as a well-known antioxidant has been reported to confer potent-free radical scavenging and anti-inflammatory properties. Therefore, the aim of the current study was to assess the influence of MSCs and GA in acute renal injury following rhabdomyolysis induced by glycerol. A total of 70 healthy rats were divided into seven groups (10 in each group): control, AKI (glycerol, intramuscular), cell therapy (AKI + intravenous injection of mesenchymal stem cells derived from adipose tissue (AMCs), AKI + AMCs + GA (50, 100, and 200mg/kg, intraperitoneally, 3days a week for 3 consecutive weeks), and positive control group (the most effective dose of gallic acid). After the treatment, rats were sacrificed; blood, urine, and kidney tissues were collected; and qualitative and quantitative parameters (including blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (SGOT), oxidative stress markers kidney function parameters) and histopathological indexes were assayed. Our results revealed that co-treatment of AMCs plus GA into AKI rats decreased BUN and creatinine and ameliorated kidney injury parameters after 3weeks. Improved oxidative stress markers such as decreased MDA and increased SOD and CAT were significant in the GA + AMCs group compared to the AMCs alone in AKI rats. Also, the histopathological appearances of AKI rats including renal tubule cavity expansion and renal tubular epithelial cell edema, and interstitial inflammation, were alleviated using GA + AMCs treatment compared to the control. The obtained results of the current study documented that antioxidants could make mesenchymal stem cells more resistant to the condition in which they are supposed to be transplanted and probably improve the efficacy of stem cell therapy in AKI patients.

Delayed onset, immunomodulation, and lifespan improvement of SOD1G93A mice after intravenous injection of human mesenchymal stem cells derived from adipose tissue

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective and progressive loss of motor neurons from the spinal cord, brain stem, and motor cortex. Although the hallmark of ALS is motor neuron degeneration, astrocytes, microglia, and T cells actively participate. Pharmacological treatment with riluzole has little effect on the lifespan of the patient. Thus, the development of new therapeutic strategies is of utmost importance. The objective of this study was to verify whether human mesenchymal stem cells (hMSCs) from adipose tissue have therapeutic potential in SOD1G93A transgenic mice. The treatment was carried out in the asymptomatic phase of the disease (10th week) by a single systemic application of ad-hMSCs (1 ×105 cells). The animals were sacrificed at the 14th week (the initial stage of symptoms) or the end-stage (ES) of the disease. The lumbar spinal cords were dissected and processed for Nissl staining (neuronal survival), immunohistochemistry (gliosis and synaptic preservation), and gene transcript expression (qRT–PCR). Behavioral analyses considering the onset of disease and its progression, neurological score, body weight, and motor control (rotarod test) started on the 10th week and were performed every three days until the ES of the disease. The results revealed that treatment with ad-hMSCs promoted greater neuronal survival (44%) than vehicle treatment. However, no effect was seen at the ES of the disease. Better structural preservation of the ventral horn in animals treated with ad-hMSCs was observed, together with decreased gliosis and greater synapse protection. In line with this, we found that the transcript levels of Hgf1 were upregulated in ad-hMSCs-treated mice. These results corroborate the behavioral data showing that ad-hMSCs had delayed motor deficits and reduced weight loss compared to vehicle animals. Additionally, cell therapy delayed the course of the disease and significantly improved survival by 20 days. Overall, our results indicate that treatment with ad-hMSCs has beneficial effects, enhancing neuronal survival and promoting a less degenerative neuronal microenvironment. Thus, this may be a potential therapy to improve the quality of life and to extend the lifespan of ALS patients.

Intra-articular Injection of Mesenchymal Stem Cells After High Tibial Osteotomy in Osteoarthritic Knee: Two-Year Follow-up of Randomized Control Trial.

Intra-articular injection of adipose-derived mesenchymal stem cell (ADMSC) after medial open-wedge high tibial osteotomy (MOWHTO) would be a promising disease-modifying treatment by correcting biomechanical and biochemical environment for arthritic knee with varus malalignment. However, there is a paucity of clinical evidence of the treatment. This randomized controlled trial (RCT) was aimed to assess regeneration of cartilage defect, functional improvement, and safety of intra-articular injection of ADMSCs after MOWHTO compared with MOWHTO alone for osteoarthritic knee with varus malalignment. This RCT allocated 26 patients into the MOWHTO with ADMSC-injection group (n = 13) and control (MOWHTO-alone) group (n = 13). The primary outcome was the serial changes of cartilage defect on periodic magnetic resonance imaging (MRI) evaluation using valid measurements until postoperative 24 months. Secondary outcomes were the 2-stage arthroscopic evaluation for macroscopic cartilage status and the postoperative functional improvements of patient-reported outcome measures until the latest follow-up. Furthermore, safety profiles after the treatment were evaluated. Cartilage regeneration on serial MRIs showed significantly better in the ADMSC group than in the control group. The arthroscopic assessment revealed that total cartilage regeneration was significantly better in the ADMSC group. Although it was not significant, functional improvements after the treatment showed a tendency to be greater in the ADMSC group than in the control group from 18 months after the treatment. No treatment-related adverse events, serious adverse events, and postoperative complications occurred in all cases. Concomitant intra-articular injection of ADMSCs with MOWHTO had advantages over MOWHTO alone in terms of cartilage regeneration with safety at 2-year follow-up, suggesting potential disease-modifying treatment for knee OA with varus malalignment.

The first experience of cord blood stem cells application in kidney transplantation: A descriptive study

Abstract. Kidney transplantation is recognized as the optimal method of end-stage kidney disease treatment, but chronic renal allograft rejection remains an unresolved issue and leads to transplanted organ function loss. Recent studies show positive effects of stem cell injections in a variety of diseases, including kidney transplantation.&#x0D; The present study aimed to analyze the first experience of umbilical cord blood stem cells application in living-related kidney transplantation in Shalimov’s National Institute of Surgery and Transplantation, give a preliminary assessment of their effectiveness and safety, evaluate the clinical course and especially the dynamics of laboratory parameters in the recipient’s postoperative period.&#x0D; Methods. The study group included 6 male, adult recipients of kidney transplants, who performed the first kidney allotransplantation from a living family donor in the Shalimov’s National Institute of Surgery and Transplantology in 2020 – 2021. Before surgery, all patients received intravenous administration of a fraction of nuclear cells from human umbilical cord blood at a dose of 2-3 x 106/kg body weight in combination with standard three-component immunosuppressive therapy. Immune system studies were performed before kidney transplantation, on the first and third days of the postoperative period, at the end of the first and second week, as well as on the first, third, sixth, and twelfth months, following kidney transplantation. Renal graft function was assessed by serum creatinine and glomerular filtration rate. Monitoring of clinical and laboratory parameters of blood and urine, the concentration of calcineurin inhibitors (C0) was carried out regularly three times a week for the first month, twice a month for 2-3 months, and once a month until the end of the year.&#x0D; Puncture biopsy of the transplanted kidney was performed three months after surgery to diagnose the pathology of the graft, namely the manifestations of acute and chronic rejection, the nature and degree of which were determined according to the Banff classification.&#x0D; The state of the immune system of the recipients was characterized by indicators of cellular and humoral immunity.&#x0D; Statistical processing of research results was performed using the statistical package StatSoft (2010) STATISTICA 9.1 for Windows StatSoft Inc, Tusla.&#x0D; Results. All patients received cord blood stem cells without complications. On the first day after surgery, an average diuresis was 9415 ± 928.1 ml. Normalization of graft function was observed on the second or third day (GFR more than 90 ml/ min/1.73 m2). There were no rejections of grafts and signs of opportunistic infections in the patients during 1 year follow-up period. Morphological studies did not reveal signs of significant pathological changes in transplanted kidneys in patients who received stem cells as induction therapy.&#x0D; The study of the state of the immune system of recipients in the dynamics, given the insufficient number of patients, requires further research.&#x0D; Conclusions. The administration of cord blood stem cells to recipients prior to kidney transplantation is safe and promotes rapid recovery of renal allograft function. There were no signs of morphological proven chronic graft rejection, which allows us to predict its long-term functioning in the future. To assess the response of the recipient's immune system to the application of cord blood stem cells requires the accumulation of additional data.

Periurethral and Intravenous Injections of Adipose-Derived Stem Cells to Promote Local Tissue Recovery in a Rat Model of Stress Urinary Incontinence

ObjectiveTo compare the effects of periurethral and intravenous injection of adipose-derived stem cells (ADSCs) on voiding function and tissue recovery in a stress urinary incontinence (SUI) rat model. MethodsSixty-four postpartum rats were randomly allocated to a normal group and the SUI model was established in 48 rats by vagina balloon dilation and bilateral ovariectomy. The SUI rats were randomized into 3 groups and received urethral injection of PBS (SUI group), periurethral injection of ADSCs (PU group), and intravenous injection of ADSCs (IV group) in 10 days after the ovariectomy. After 1, 7, and 14 days, ADSCs were tracked in urethra specimen. The urinary function of the remaining rats was analyzed at day 28, and urethral tissues were harvested for Western blotting and histochemical analyses. ResultsAlpha smooth muscle actin, myosin heavy chain, vascular endothelial growth factor, and neurofilament protein expression was increased in the IV and PU groups. Voiding function was also improved, with no significant differences between the IV and PU groups. The cell retention rate in rat urethral tissues was higher in the PU group than that in the IV group. Compared with the IV group, myosin heavy chain, vascular endothelial growth factor, neurofilament and transforming growth factor-β1 (TGF-β1)/Smad pathway protein expression levels were significantly higher in the PU group, while alpha smooth muscle actin expression was significantly lower (P < .05). ConclusionPeriurethral and intravenous injection of ADSCs induces different degrees of recovery of the urethral sphincter, cytokine secretion levels and cell retention rates in the urethral tissues in SUI rats, however, there was no significant difference in 2 methods.

New frontiers for cartilage repair, joint preservation and prevention

Damaged cartilage is seen with increasing frequency after joint trauma, alone or in combination with other joint injuries. A poor healing of injured cartilage leads to great disability and pain and could by time develop into osteoarthritis (OA). During the last 50 years, new cartilage repair techniques have appeared with more or less satisfactory results. In this presentation, the focus is to present areas that we might see more of in the future. It is important to separate local cartilage repair from a generalized loss of cartilage as OA. For both conditions, a base is a non-operative treatment with focus on new techniques of physiotherapy. Intra-articular injections of stem cells are mainly for OA as a source of growth factors but also as an adjunct to improve repair quality when using intrinsic local repairs. The use of in vitro manipulated chondrogeneic cells has decreased during the last decade due to strict regulations and high production costs. Instead, the focus is now on 1 stage procedures with autologous chondrogeneic cells but also more use of allogeneic chondrogeneic cells either alone or combined with autologous cells. An area of interest is the 3D technology used for bio printing of the lesions. Concomitant injuries are taken care as part of joint preservation and we need to better use preventive means to avoid future injuries. The assembled knowledge of joint repair, preservation and joint damage prevention may help us to reach the goal of going from local repair to a local regeneration become feasible.

Injection of adipose stem cells in the treatment of rotator cuff disease - a narrative review of current evidence.

The purpose of this study is to summarize evidence for the use of adipose stem cell (ASC) injections in the treatment of rotator cuff tears (RCT) and identify future areas of study. A thorough literature search was performed to identify studies investigating the use of ASC injections in the treatment of RCTs. Among animal trials, it is unclear whetherASCs are of benefit for rotator cuff repair. In clinical trials, ASC injection may reduce retear rate with otherwise equivocal clinical outcomes. Although ASC injection may be safe, the literature does not provide a clear consensus as to the efficacy of ASC injections, nor does it delineate which patients would benefit most from this treatment.