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The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration.
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Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has had an unprecedented impact on people around the world, particularly those who were suffering from autoimmune rheumatic diseases (AIRDs). The world community acknowledges the significance of COVID-19 vaccination in patients with autoimmune disorders and emphasizes the priority of this category to receive vaccination over the general population. Although many studies have been published since the first phases of vaccination all over the world, multiple related factors still need to be further investigated. Material and methods: We investigated the COVID-19 vaccination status in patients with AIRDs, by performing a cross-sectional, interview-based study filled in by patients attending their clinics in the Astana city, capital of Kazakhstan, from April to July 2023. The survey questionnaire consisted of a set of questions, concerning patient characteristics, treatment details, accepted vaccines and characteristics of COVID-19 infection. The study objectives were to evaluate vaccine hesitancy, adverse effects, breakthrough infections and flare of underlying rheumatic disease in this population subgroup. Results: There were 193 participants, with a median age of 50.3 ±12.9 years. Among them, 62 (32.1%) were vaccinated with at least single dose of vaccine, 16 (25.8%) of whom were fully vaccinated. The commonest (89; 68%) reason for vaccine hesitancy was a fear of autoimmune disease worsening. Vaccine-related adverse effects (AEs) were reported by 66.7% of patients. We found that vaccination provoked AIRD exacerbation in 19% of patients with AEs. Eight patients reported flare of pre-existing rheumatic disease after vaccination. The incidence of breakthrough infections was similar in the groups of vaccinated individuals (n = 12), 12.9% of whom were partially and 6.5% fully vaccinated. Conclusions: The vaccination was found to be safe in patients with rheumatic diseases. Fear of autoimmune status was the major reason for vaccine reluctance. All reported adverse events were minor. The minority subgroup within the sample had subsequent breakthrough infections or autoimmune disease flare-ups.
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Limonium (L.) gmelinii is a valuable pharmacopoeial Kazakhstani plant. Several studies have reported on the various biological activities of the plant. The purpose of our research was to study and compare the extraction yields, immunomodulatory activities, and chemical compositions of extracts from the above-ground parts of L. gmelinii obtained via conventional extraction (CE; Extract 1) and ultrasound-assisted extraction (UAE; Extract 2). The extracts were characterized by a considerable number of polyphenols and flavonoids: 378.1 ± 4.5 and 382.2 ± 3.3 GAE mg/g, and 90.22 ± 2.8 and 94.61 ± 1.9 QE mg/g in Extract 1 and Extract 2, respectively. Extract 2 had a slightly higher extraction yield (33.5 ± 2.4%) than Extract 1 (30.2 ± 1.6%). Liquid Chromatography-Diode-Array Detection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) revealed the presence of 54 biologically active compounds in both extracts. It was shown that the studied extracts stimulate the secretion of TNF-α and IL-6 by intact mouse peritoneal macrophages and splenic lymphocytes, whilst they have an inhibitory effect on the secretion of these cytokines by activated immune cells. Both extracts demonstrated similar patterns of stimulation and inhibition in a splenocyte proliferation assay. Altogether, the L. gmelinii extracts obtained via CE and UAE might be suggested as effective immunomodulatory agents. The application of UAE for this purpose seems to be more efficient with a view of obtaining of a highly potent extract in a much shorter time.
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Atherosclerosis (AS) is an inflammatory disease involving multiple factors in its initiation and development. In recent years, the potential application of mesenchymal stem cells (MSCs) for treating AS has been investigated. This study examined the effect of TNF-α preconditioning on MSCs' therapeutic efficacy in treating AS in ApoE KO mice. TNF-α-treated MSCs were administered to high-fat diet-treated ApoE KO mice. Cytokine and serum lipid levels were measured before and after treatment. Cryosections of the atherosclerotic aorta were stained with Oil-Red-O, and the relative areas of atherosclerotic lesions were measured. The level of Tregs were increased in TNF-α-MSC-treated animals compared to the MSCs group. In addition, the systemic administration of TNF-α-MSCs to ApoE KO mice reduced the level of proinflammatory cytokines such as TNF-α and IFN-γ and increased the level of the immunosuppressive IL-10 in the blood serum. Total cholesterol and LDL levels were decreased, and HDL levels were increased in the TNF-α-MSCs group of ApoE KO mice. A histological analysis showed that TNF-α-MSCs decreased the size of the atherosclerotic lesion in the aorta of ApoE KO mice by 38%, although there was no significant difference when compared with untreated MSCs. Thus, our data demonstrate that TNF-α-MSCs are more effective at treating AS than untreated MSCs.
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Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent preclinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications.
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The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising therapeutic strategy for osteochondral defects regeneration. In this study, we fabricated a heparin-conjugated fibrin (HCF) hydrogel with synovium-derived mesenchymal stem cells (SDMSCs), transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-4 (BMP-4) to repair osteochondral defects in a rabbit model. An in vitro study showed that HCF hydrogel exhibited good biocompatibility, a slow degradation rate and sustained release of TGF-ß1 and BMP-4 over 4 weeks. Macroscopic and histological evaluations revealed that implantation of HCF hydrogel with SDMSCs, TGF-ß1 and BMP-4 significantly enhanced the regeneration of hyaline cartilage and the subchondral bone plate in osteochondral defects within 12 weeks compared to hydrogels with SDMSCs or growth factors alone. Thus, these data suggest that combined delivery of SDMSCs with TGF-ß1 and BMP-4 in HCF hydrogel may synergistically enhance the therapeutic efficacy of osteochondral defect repair of the knee joints.
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Medicines, their safety, effectiveness and quality are indispensable factors of national security, important on a global scale. The COVID-19 pandemic has once again emphasized the importance of improving the immune response of the body in the face of severe viral infections. Plants from the Salvia L. genus have long been used in traditional medicine for treatment of inflammatory processes, parasitic diseases, bacterial and viral infections. The aim of the current study was to evaluate the immunomodulatory effects of plant extracts LS-1, LS-2 from Salvia deserta Schang. and LS-3, LS-4 from Salvia sclarea L. plants growing in southern Kazakhstan by conventional and ultrasonic-assisted extraction, respectively. The cytotoxic effects of the named sage extracts on neonatal human dermal fibroblasts (HDFn) were evaluated using the MTT assay. Immunomodulatory effects of the studied extracts were compared by examining their influence on pro-inflammatory cytokine secretion and phagocytic activity of murine immune cells. Depending on the physiological state of the innate immune cells, sage extracts LS-2 and LS-3 had either a stimulating effect on inactivated macrophages or suppressed cytokine-producing activity in LPS-activated macrophages. The greatest increase in TNF-α secretion was found after treatment of spleen T lymphocytes with sage extract LS-2, obtained by ultrasonic-assisted extraction.
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Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.
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Células-Tronco Mesenquimais , Diferenciação Celular , ImunomodulaçãoRESUMO
Cryogels are a unique macroporous material for tissue engineering. In this work, we study the effect of hyaluronic acid on the physicochemical properties of cryogel as well as on the proliferation of a 3D model of mesenchymal stem cells. The functional groups of the synthesized cryogels were identified using Fourier transform infrared spectroscopy. With an increase in the content of hyaluronic acid in the composition of the cryogel, an increase in porosity, gel content and swelling behavior was observed. As the hyaluronic acid content increased, the average pore size increased and more open pores were formed. Degradation studies have shown that all cryogels were resistant to PBS solution for 8 weeks. Cytotoxicity assays demonstrated no toxic effect on viability of rat adipose-derived mesenchymal stem cells (ADMSCs) cultured on cryogels. ADMSC spheroids were proliferated on scaffolds and showed the ability of the cryogels to orient cell differentiation into chondrogenic lineage even in the absence of inductive agents. Thus, our results demonstrate an effective resemblance to extracellular matrix structures specific to cartilage-like microenvironments by cryogels and their further perspective application as potential biomaterials.
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Background and Objectives: Homogeneous and xenogenic bioengineering structures are actively used as wound coatings in treatment of burns and have already shown their effectiveness. Nevertheless, the disadvantage of such dressings is their high cost. This issue is particularly challenging for developing countries in which the incidence of burns is the highest one. With such needs taken into account, the research team developed and clinically tested a new wound coating based on decellularized bovine peritoneum (DBP). Materials and Methods: A multicenter randomized clinical trial was conducted to evaluate DBP. The following variables were considered in the research study: the number of inpatient days, the number of dressing changes, the level of pain experienced during dressing changes, and the condition of wounds at the time of the follow-up examination. Results: The research involved 68 participants. It was found that the patients who were treated with a DBP experienced less pain with less changes of dressings. However, the number of inpatient days and wound healing failed to demonstrate statistically significant difference compared to the control group. Conclusions: In the given research, DBP showed efficacy in improving patients' quality of life by reducing pain and the number of dressings' changes. However, when comparing this research study with the studies of other animal-derived wound coverings, there were a number of differences and limitations in the parameters. Thus, the results requires further study for a greater comparability of data. Given the above, we expect that DBP will become an inexpensive and effective treatment for burns in developing countries.
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Queimaduras , Peritônio , Animais , Queimaduras/terapia , Bovinos , Xenoenxertos , Humanos , Dor , Qualidade de Vida , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
In vivo biotinylation using wild-type and mutants of biotin ligases is now widely applied for the study of cellular proteomes. The commercial availability of kits for the highly efficient purification of biotinylated proteins and their excellent compatibility with LC-MS/MS protocols are the main reasons for the choice of biotin ligases. Since they are all enzymes, however, just a very low expression in cells is required for experiments. Therefore, it can be difficult to perform the quantifications of these enzymes in various samples. Traditional methods, such as western blotting, are not always fit for the detection of the expression levels. Therefore, real-time qRT-PCR, a technology that is more sensitive, was used in this study to quantify the expression of BirA fusions. Using this method, we detected high expression levels of BirA fusions in models of interactions of pluripotency transcription factors to carry out their relative quantification. We also found the absence of the competing endogenous proteins SOX2 and OCT4, as well as no cross-reactivity between BAP/BirA and the endogenous biotinylation system in HEK293T cells. Thus, these data indicated that the high level of biotinylation is due to the in vivo interaction of BAP-X and BirA-Y (X,Y = SOX2, OCT4) in the cell rather than their random collision, a big difference in the expression level of BirA fusions across samples or endogenous biotinylation.
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Mesenchymal stem cells (MSCs) have great potential to differentiate into various types of cells, including but not limited to, adipocytes, chondrocytes and osteoblasts. In addition to their progenitor characteristics, MSCs hold unique immunomodulatory properties that provide new opportunities in the treatment of autoimmune diseases, and can serve as a promising tool in stem cell-based therapy. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that deteriorates quality and function of the synovium membrane, resulting in chronic inflammation, pain and progressive cartilage and bone destruction. The mechanism of RA pathogenesis is associated with dysregulation of innate and adaptive immunity. Current conventional treatments by steroid drugs, antirheumatic drugs and biological agents are being applied in clinical practice. However, long-term use of these drugs causes side effects, and some RA patients may acquire resistance to these drugs. In this regard, recently investigated MSC-based therapy is considered as a promising approach in RA treatment. In this study, we review conventional and modern treatment approaches, such as MSC-based therapy through the understanding of the link between MSCs and the innate and adaptive immune systems. Moreover, we discuss recent achievements in preclinical and clinical studies as well as various strategies for the enhancement of MSC immunoregulatory properties.
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Artrite Reumatoide/terapia , Células-Tronco Mesenquimais/citologia , Animais , Artrite Reumatoide/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Sistema Imunitário/imunologia , Imunomodulação/imunologia , Inflamação/imunologia , Inflamação/terapia , Células-Tronco Mesenquimais/imunologiaRESUMO
Three-dimensional (3D) bioprinting is a promising technology to establish a 3D in vitro hepatic model that holds great potential in toxicological evaluation. However, in current hepatic models, the central area suffers from hypoxic conditions, resulting in slow and weak metabolism of drugs and toxins. It remains challenging to predict accurate drug effects in current bioprinted hepatic models. Here, we constructed a hexagonal bioprinted hepatic construct and incorporated a spinning condition with continuous media stimuli. Under spinning conditions, HepG2 cells in the bioprinted hepatic construct exhibited enhanced proliferation capacity and functionality compared to those under static conditions. Additionally, the number of spheroids that play a role in boosting drug-induced signals and responses increased in the bioprinted hepatic constructs cultured under spinning conditions. Moreover, HepG2 cells under spinning conditions exhibited intensive TGFß-induced epithelial-to-mesenchymal transition (EMT) and increased susceptibility to acetaminophen (APAP)-induced hepatotoxicity as well as hepatotoxicity prevention by administration of N-acetylcysteine (NAC). Taken together, the results of our study demonstrate that the spinning condition employed during the generation of bioprinted hepatic constructs enables the recapitulation of liver injury and repair phenomena in particular. This simple but effective culture strategy facilitates bioprinted hepatic constructs to improve in vitro modeling for drug effect evaluation.
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Biomimética , Bioimpressão/instrumentação , Proliferação de Células , Fígado/patologia , Modelos Biológicos , Impressão Tridimensional/estatística & dados numéricos , Engenharia Tecidual , Acetaminofen/toxicidade , Acetilcisteína/farmacologia , Analgésicos não Narcóticos/toxicidade , Sequestradores de Radicais Livres/farmacologia , Células Hep G2 , Humanos , Hidrogéis , Técnicas In Vitro , Fígado/efeitos dos fármacos , Alicerces Teciduais/química , Testes de ToxicidadeRESUMO
Atherosclerosis is a multifactorial and complex disease involving the arterial intima of the circulatory system. The main risk factors of atherosclerosis are diabetes mellitus, hypertension, hyperlipidemic states, smoking, mental stress, unhealthy diet, and a lack of physical activity. Recent studies have shown that dyslipidemia, inflammation and immune cells are involved in all stages of the development of atherosclerosis. Mesenchymal stem cells are a heterogeneous subset of multipotent cells that can be isolated from nearly all human organs and tissues, and they possess both regenerative and immunomodulatory properties. Recent studies have shown that mesenchymal stem cells are able to provide immunosuppressive, regenerative, and atheroprotective effects by reducing dyslipidemia, inflammation and inhibiting endothelial cell dysfunction and plaque formation during the development of atherosclerosis in animal models. Based on these beneficial effects, mesenchymal stem cells are considered a promising alternative therapeutic approach for the effective treatment of atherosclerosis. In this review, we summarize the current findings on potential applications of mesenchymal stem cells for preventing and regressing atherosclerosis as well as discuss strategies for improving the efficacy of mesenchymal stem cell-based therapy.
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Aterosclerose , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Aterosclerose/terapia , Células Endoteliais , Humanos , Imunomodulação , Inflamação/terapiaRESUMO
Despite the high regenerative capacity of bone tissue, there are some cases where bone repair is insufficient for a complete functional and structural recovery after damage. Current surgical techniques utilize natural and synthetic bone grafts for bone healing, as well as collagen sponges loaded with drugs. However, there are certain disadvantages associated with these techniques in clinical usage. To improve the therapeutic efficacy of bone tissue regeneration, a number of drug delivery systems based on biodegradable natural and synthetic polymers were developed and examined in in vitro and in vivo studies. Recent studies have demonstrated that biodegradable polymers play a key role in the development of innovative drug delivery systems and tissue engineered constructs, which improve the treatment and regeneration of damaged bone tissue. In this review, we discuss the most recent advances in the field of polymer-based drug delivery systems for the promotion of bone tissue regeneration and the physical-chemical modifications of polymers for controlled and sustained release of one or more drugs. In addition, special attention is given to recent developments on polymer nano- and microparticle-based drug delivery systems for bone regeneration.
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Pericytes possess high multipotent features and cell plasticity, and produce angiogenic and neurotrophic factors that indicate their high regenerative potential. The aim of this study was to investigate whether transplantation of adipose-derived pericytes can improve functional recovery and neurovascular plasticity after ischemic stroke in rats. Rat adipose-derived pericytes were isolated from subcutaneous adipose tissue by fluorescence-activated cell sorting. Adult male Wistar rats were subjected to 90 min of middle cerebral artery occlusion followed by intravenous injection of rat adipose-derived pericytes 24 h later. Functional recovery evaluations were performed at 1, 7, 14, and 28 days after injection of rat adipose-derived pericytes. Angiogenesis and neurogenesis were examined in rat brains using immunohistochemistry. It was observed that intravenous injection of adipose-derived pericytes significantly improved recovery of neurological function in rats with stroke compared to phosphate-buffered saline-treated controls. Immunohistochemical analysis revealed that the number of blood capillaries was significantly increased along the ischemic boundary zone of the cortex and striatum in stroke rats treated with adipose-derived pericytes. In addition, treatment with adipose-derived pericytes increased the number of doublecortin positive neuroblasts. Our data suggest that transplantation of adipose-derived pericytes can significantly improve the neurologic status and contribute to neurovascular remodeling in rats after ischemic stroke. These data provide a new insight for future cell therapies that aim to treat ischemic stroke patients.
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Tecido Adiposo/citologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Pericitos/transplante , Animais , Linhagem da Célula , Forma Celular , Células Clonais , Proteína Duplacortina , Infarto da Artéria Cerebral Média/patologia , AVC Isquêmico/patologia , Masculino , Neovascularização Fisiológica , Neurogênese , Ratos WistarRESUMO
Biomechanical properties of mammalian bones, such as strength, toughness, and plasticity, are essential for understanding how microscopic-scale mechanical features can link to macroscale bones' strength and fracture resistance. We employ Brillouin light scattering (BLS) microspectroscopy for local assessment of elastic properties of bones under compression and the efficacy of the tissue engineering approach based on heparin-conjugated fibrin (HCF) hydrogels, bone morphogenic proteins, and osteogenic stem cells in the regeneration of the bone tissues. BLS is noninvasive and label-free modality for probing viscoelastic properties of tissues that can give information on structure-function properties of normal and pathological tissues. Results showed that MCS and BPMs are critically important for regeneration of elastic and viscous properties, respectively, HCF gels containing combination of all factors had the best effect with complete defect regeneration at week nine after the implantation of bone grafts and that the bones with fully consolidated fractures have higher values of elastic moduli compared with defective bones.
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Osso e Ossos , Elasticidade/fisiologia , Espalhamento de Radiação , Análise Espectral/métodos , Animais , Regeneração Óssea/fisiologia , Osso e Ossos/química , Osso e Ossos/citologia , Osso e Ossos/diagnóstico por imagem , Células Cultivadas , Desenho de Equipamento , Luz , Células-Tronco Mesenquimais/citologia , Microscopia Confocal , Coelhos , Radiografia , Análise Espectral/instrumentação , Engenharia TecidualRESUMO
INTRODUCTION: The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. RESULTS: At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. CONCLUSIONS: It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.
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Infarto do Miocárdio/imunologia , Miocárdio/imunologia , Imunidade Adaptativa , Animais , Humanos , Imunidade Inata , Inflamação , Macrófagos/imunologia , Monócitos/imunologia , Infarto do Miocárdio/patologia , Miocárdio/patologiaRESUMO
Mesenchymal stem cells (MSCs) have attracted the attention of researchers and clinicians for their ability to differentiate into a number of cell types, participate in tissue regeneration, and repair the damaged tissues by producing various growth factors and cytokines, as well as their unique immunoprivilege in alloreactive hosts. The immunomodulatory functions of exogenous MSCs have been widely investigated in immune-mediated inflammatory diseases and transplantation research. However, a harsh environment at the site of tissue injury/inflammation with insufficient oxygen supply, abundance of reactive oxygen species, and presence of other harmful molecules that damage the adoptively transferred cells collectively lead to low survival and engraftment of the transferred cells. Preconditioning of MSCs ex vivo by hypoxia, inflammatory stimulus, or other factors/conditions prior to their use in therapy is an adaptive strategy that prepares MSCs to survive in the harsh environment and to enhance their regulatory function of the local immune responses. This review focuses on a number of approaches in preconditioning human MSCs with the goal of augmenting their capacity to regulate both innate and adaptive immune responses.
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INTRODUCTION: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits. MATERIAL AND METHODS: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days. RESULTS: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC-treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage. CONCLUSION: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.