Injection Of Autologous Mesenchymal Stem Cells Research Articles

Autologous Mesenchymal Stem Cell Treatment is Consistently Effective for the Treatment of Knee Osteoarthritis: The Results of a Systematic Review of Treatment and Comparison to a Placebo Group.

Background: Numerous studies have used autologous mesenchymal stem cell injections (AMSCI) to treat osteoarthritis. We hypothesized that AMSCI is an effective osteoarthritis treatment with increasing efficacy at higher doses. Methods: We conducted a PubMed search for human clinical studies using AMSCI for the treatment of osteoarthritis (OA) and a second search for placebo arms of injectate OA treatment. Inclusion criteria included treatment outcomes ratings both pre-treatment and at least 6 months post-treatment. Results: 45 AMSCI cohorts from 34 studies met criteria. All AMSCI cohorts showed improvement at mean 15.3 months post-treatment. Mean WOMAC and VAS scores improved at 6-months and at final follow-up (p < 0.0001 for all). Scores > 2 years were also significant (WOMAC p = 0.001/VAS p = 0.004). Results greatly exceeded the minimal clinically important difference (MCID) at each time point. AMSCI improvement also substantially exceeded previously published 6-month placebo-treatment improvement. No dose–response relationship was seen. AMSCI cohorts showed continuing improvement ≥ 6 months, and continued upward at one year. Placebo scores were already trending downward by 6 months. Conclusions: AMSCI is a consistently significantly effective treatment for osteoarthritis. It should no longer be stated that data is insufficient to establish AMSCI efficacy for OA. Given its excellent safety profile, AMSCI should be widely used for the treatment of osteoarthritis.

Investigating the Effect of Mesenchymal Stem Cells on Peripheral Nerve Repair with Quantitative Methods

Objective: The aim was to research the possible effects of bone marrow stromal cells on the effective method for peripheral nerve injuries of end-in-end repair for sciatic nerves using quantitative histologic methods.Methods: Five adult male New Zealand rabbits had both sciatic nerves cut and then the end-in-end repair technique performed. Then while nothing was administered to the left side, the right side had autologous mesenchymal stem cell injection from previously cultured material administered. Four weeks later the repair area was removed, and sections were stained with S100 and CD31 antibodies. Stained sections were investigated for Schwann cells and vessels. Evaluations of the left and right sides were made by comparing their Schwann cell density and vessel density determined by estimating their volume fractions, separately.Results: The repair areas on both sides showed no significant differences for the degree of immunoreactivity for S100 and CD31 (p=0.003). But the volume fractions of Schwann cells and vessels within the repair areas were found to be increased for the cell-treated nerves, but statistically there was no difference for vessels (p=0.073).Conclusion: These results support the findings already reported in the literature, that increased Schwann cell density will probably promote regeneration of the peripheral nerve.

The Assessment of the Efficiency of Cell Therapy of Experimental Liver Cirrhosis by Means of Ultrasound Examination

Objective: to determine the relevance of ultrasound examination in diagnostics and assessment of the efficiency of cell therapy of experimental liver cirrhosis in rabbits.Material and methods. The experiment was performed on white Californian rabbits (n = 45). Liver cirrhosis was modelled by means of subcutaneous injections of 50 % solution of carbon tetrachloride according to the scheme. Cell therapy was performed by means of a single intraportal injection of autologous mesenchymal stem cells (MSCs) at an amount of 5 × 106 cells per kg. During the experiment all the animals were performed the ultrasound examination of the abdominal cavity, as well as the morphological analysis of liver tissue samples.Results. After 5 months of the liver cirrhosis modeling, the anteroposterior liver size and diameter of the portal vein in group 2 and group 3 were statistically larger than in group 1 (р &lt; 0.001, Mann-Whitney test). There was no statistical difference in the anteroposterior liver size (р = 0.38) and diameter of the portal vein (р = 0.36) between group 2 and group 3. 1 month after the injection of autologous MSCs, the rabbits of group 3 detected some improvement of the echimage of the damaged liver, which was also reflected in a statistically significant decrease of the liver size by 8.2 % (р &lt; 0.01, Wilcoxon test) and diameter of the portal vein by 23 % (р &lt; 0.001) in comparison with the indicators before the injection of MSCs.Conclusion. The ultrasound examination in the present study has proved itself to be a reliable method of intravital diagnostics of pathological changes in the conditions of a chronic experiment, and also has revealed a positive impact of cell therapy on liver cirrhosis in the rabbits. The obtained data were confirmed by the morphological methods of the analysis of the liver tissue samples of the animals during the experiment.

Injections for Knee Osteoarthritis: Corticosteroids, Viscosupplementation, Platelet-Rich Plasma, and Autologous Stem Cells

This article reviews the benefits of corticosteroid, viscosupplementation, platelet-rich plasma, and autologous mesenchymal stem cell injections for the treatment of patients with knee osteoarthritis. Integrating injections into both clinical and surgical practices is complicated given existing health insurance reimbursement policies. This review describes the outcomes associated with these interventions and appropriate methods of navigating the existing reimbursement pathways to help providers implement these treatments into their practices.

Mesenchymal stem cells require the peripheral immune system for immunomodulating effects in animal models of multiple sclerosis.

Mesenchymal stem cells require the peripheral immune system for immunomodulating effects in animal models of multiple sclerosis.

Mesenchymal stem cells injection with core decompression in the treatment of Kienbock disease

Abstract Treatment of Kienbock disease (the avascular necrosis of the lunate) is a matter of debate. Current surgical modalities have their limitations and potential complications. Those modalities are also not based on pathophysiology of the disease. Here we introduce a novel therapeutic option by combining the autologous mesenchymal stem cell injection and the core decompression procedure in the treatment of Kienbock disease. We hypothesized that micro-drilling of the lunate removes the necrotic tissue and induces new bone formation while injection of mesenchymal stem cell provides a poll of multi-potent cells to replace the dead bone. This new treatment modality would provide synergistic effects of the two therapeutic options beside lower potential complications while eliminating the need for current surgical operations.

Safety of Intraperitoneal Injection of Adipose Tissue‐Derived Autologous Mesenchymal Stem Cells in Cats

BackgroundChronic inflammatory diseases are common in cats and mesenchymal stem cells (MSC) are a promising therapeutic approach for management of these disorders. The purpose of this study was to evaluate the safety of intraperitoneal injection of MSC in cats.HypothesisIntrapertioneal injection of autologous MSC in cats is safe.AnimalsTen healthy adult purpose‐bred cats.MethodsMesenchymal stem cells were isolated from subcutaneous adipose tissue collected during ovariohysterectomy and characterized for expression of CD90, CD105 and CD44 and trilineage differentiation. Three weeks postoperatively a complete blood count, serum chemistry profile, urinalysis, and abdominal ultrasound were performed. Five cats then received 1 × 106 of autologous MSC/kg of body weight intraperitoneally with ultrasound guidance; 5 additional cats were sham injected. Cats were monitored for 6 weeks with daily physical examinations and weekly clinicopathological evaluations. Abdominal ultrasonography was repeated at weeks 1 and 5 after injection.ResultsSerious adverse effects were not observed in any MSC‐injected cat. Two animals developed transient lethargy and decreased activity. Jejunal lymph node size was increased in MSC‐injected cats compared to controls at weeks 1 (1.38 ± 0.25 versus 0.88 ± 0.25 cm2; P = .036) and 5 (1.75 ± 0.82 versus 0.79 ± 0.12 cm2; P = .047). A hyperechoic renal segmental cortical lesion was observed in 1 MSC‐injected cat.Conclusions and Clinical RelevanceIntraperitoneal MSC injection was well tolerated with only mild, self‐limiting adverse effects being observed in 2 cats. This route provides a safe means of administration for cell‐based treatment in cats.

Anti-inflammatory effects of equine adipose-derived mesenchymal stem cells for bone fracture in thoroughbred racehorses

Bone fractures are most often seen in racetrack horses because of the high level of intensity in racing. These issues are the main cause of decreased performance in racehorses. Mesenchymal stem cells (MSCs) have been explored to improve intra-articular therapy in racehorses. MSCs are essential for the repair and regeneration of damaged tissues. In this study, the effect of intra-articular injection of MSCs in racehorses was investigated. Before accessing the MSC therapy, synovial fluids were obtained from the fracture site of racehorses, and adipose tissue was collected for MSC isolation. Using the MSC specific marker, adipose tissue-derived MSCs were identified. The racehorses received intra-articular injection of autologous MSCs (or allogeneic) (3 × 10 7 cells/3 mL). After 1 or 2 weeks, synovial fluids were collected from racehorses. To test the effect of MSC injection using ELISA, we analyzed inflammatory factors from the untreated samples compared to MSC-treated samples of racehorses. The level of pro-inflammatory factors (interleukin-1 β and prostaglandin E2) was significantly decreased in synovial fluids of MSC-injected racehorses, compared to before accessing the MSC therapy, whereas, the level of anti-inflammatory factor (interleukin-10) was higher than prior to accessing the MSC therapy. Further studies are needed to investigate the anti-inflammatory mechanism of MSC in racehorses.

The use of mesenchymal stem cells (MSCs) for cartilage regeneration in knee osteoarthritis

BACKGROUND: Knee osteoarthritis (OA) represents an enormous societal burden. Yet no approved procedure prevents the progressive destruction of the articular cartilage. AIM: This review aims to update the use of mesenchymal stem cells (MSCs) for cartilage regeneration in knee OA. METHODS: A PubMed (MEDLINE) search related to MSCs and knee OA were analyzed. Articles related to the use of MSCs in knee OA were searched using the following key words: knee OA stem cells and stifle joint stem cells. A total of 210 reports were found but only 19 very selected and reviewed. The main criterion for selection was that the articles were focused in the aforementioned question. RESULTS: Local delivery (intraarticular injection) of autologous MSCs has produced promising outcomes in 16 experimental models of knee OA. However, only 3 low-quality clinical studies have been reported so far on the role of MSCs injections in knee OA. Study design weakness prevented effective comparison of the efficacy of MSC injections with that of other treatments for relief of pain and other outcomes in human knee OA. The consistency of evidence of the clinical studies was low because of many uncontrolled variables. CONCLUSIONS: Animal experiments suggest that intraarticular injections of autologous MSCs can have the potential to promote cartilage regeneration in knee OA. Taking into account the low quality of the data reported in clinical studies, my conclusion is that intraarticular injections of autologous MSCs in knee OA is a treatment that is still experimental.

A preliminary report on stem cell therapy for neuropathic pain in humans.

ObjectiveMesenchymal stem cells (MSCs) have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i) injections of autologous MSCs can reduce human neuropathic pain and ii) evaluate the safety of the procedure.MethodsTen subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i) pain intensity measured by standard numerical rating scale from 0–10 and ii) daily dosage requirements of antineuropathic pain medication.ResultsSubjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years) with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites). Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58) and at 6 months had decreased to 4.3 (SD 3.28), P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student’s t-test).ConclusionThis preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain significantly reduced pain intensity at 6 months and is a safe and well tolerated intervention.

The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)-induced failing hearts. Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups (P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups (P = 0.927). Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.

Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

IntroductionThis is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis.Case reportsStem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed.ConclusionsThe MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

Interleukin (IL)-10 Induced by CD11b+ Cells and IL-10-Activated Regulatory T Cells Play a Role in Immune Modulation of Mesenchymal Stem Cells in Rat Islet Allografts

Mesenchymal stem cells (MSCs) are suggested to be immune modulators because of their therapeutic potential in transplantation. In the present study, we evaluated the therapeutic potential of autologous MSCs for preventing graft rejection after allogeneic rat islet transplantation. We assessed the ability of MSCs to elicit an antiproliferative response in alloreactive lymphocytes and tested the immunosuppressive effect of MSCs in allogeneic islet transplantation. In islet allotransplantation, injection of autologous MSCs or a subtherapeutic dose of cyclosporine A (CsA; 5 mg/kg) alone did not prolong allograft survival. However, graft survival was attained for >100 d in 33% of autologous MSC-plus-CsA-treated recipients, indicating that graft acceptance was achieved in a subgroup of allograft recipients. Splenocytes from autologous MSC-plus-CsA-treated rats exhibited a reduced mixed lymphocyte reaction (MLR)-proliferative response to donor stimulators and increased interleukin (IL)-10 release. Interestingly, after excluding host CD11b(+) cells, splenic T cells from autologous MSC-plus-CsA-treated rats did not produce IL-10 or did not inhibit proliferative responses under the same conditions. The use of autologous MSC-plus-CsA downregulated immune responses, inducing donor-specific T-cell hyporesponsiveness by reducing the production of proinflammatory cytokines and inducing antiinflammatory cytokine production, especially that of IL-10, during the early posttransplantation period. T-regulatory cells made a contribution at a later phase. In conclusion, the combined use of autologous MSCs and low-dose CsA exerted a synergistic immunosuppressive effect in an islet allograft model, suggesting a role for autologous MSCs as an immune modulator.

Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I–II clinical trial

End-stage liver disease is a medical problem with high morbidity and mortality. We have investigated the feasibility, safety, and efficacy of using autologous mesenchymal stem cells (MSCs) as a treatment. Eight patients (four hepatitis B, one hepatitis C, one alcoholic, and two cryptogenic) with end-stage liver disease having Model for End-Stage Liver Disease score > or =10 were included. Autologous MSCs were taken from iliac crest. Approximately, 30-50 million MSCs were proliferated and injected into peripheral or the portal vein. Liver function and clinical features were evaluated at baseline and 1, 2, 4, 8, and 24 weeks after injection. Treatment was well tolerated by all patients. Liver function improved as verified by the Model for End-Stage Liver Disease score, which decreased from 17.9+/-5.6 to 10.7+/-6.3 (P<0.05) and prothrombin complex from international normalized ratio 1.9+/-0.4 to 1.4+/-0.5 (P<0.05). Serum creatinine decreased from 114+/-35 to 80+/-18 micromol/l (P<0.05). Serum albumin changed from 30+/-5 to 33+/-5 g/l and bilirubin from 46+/-29 to 41+/-31 micromol/l. No adverse effects were noted. Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.

Evaluation of the effect of autologous mesenchymal stem cell injection in a large‐animal model of bilateral kidney ischaemia reperfusion injury

Adult mesenchymal stem cells (MSC) have been proven to be of benefit to the kidney in different experimental models of renal injuries. All studies have been performed in valuable rodent models, but the relevance of these results to large mammals and ultimately, to humans remains unknown. Therefore, the aim of this study was to investigate the effect of MSC transplantation in an alternative ovine large-animal model of bilateral kidney ischaemia reperfusion injury. Sheep were divided into three groups: one sham-operated group and two groups submitted to renal bilateral ischaemia for 60 min. Animals with ischaemia reperfusion injury were treated with injection of autologous MSCs or with vehicle medium. The model sheep presented with renal histological manefestations that closely resembled lesions seen in patients. Transplanted MSCs were found in glomeruli but not in tubules and did not express glomerular cell markers (podocin, von Willebrand factor), but functional evaluation showed no beneficial effect of MSC infusion. Morphological and molecular analyses corroborated the functional results. MSCs did not repair kidney parenchyma and failed to modulate cell death and proliferation or cytokine release (tumour necrosis factor-alpha, vascular endothelial growth factor alpha (VEGF-alpha), Bcl-2, caspase). In this unique autologous large-animal model, MSCs did not exhibit reparative or paracrine protective properties.