Transplantation Of Multipotent Mesenchymal Stromal Cells Research Articles

The effects of human umbilical cord-derived multipotent mesenchymal stromal cells transplantation in mice of different strains with an experimental model of parkinsonism

One of the promising directions in cell therapy for Parkinson's disease or parkinsonism is the transplantation of multipotent mesenchymal stromal cells from various sources, including human umbilical cord (hUC-MMSCs), the effectiveness of which may depend on the recipient's genotype. Objective. To compare the impact of transplanted MMSC-P on behavior, T-lymphocytes, and macrophages in the brain and lymphoid organs of mice from different lines with a toxic model of parkinsonism. Materials and methods. Adult (6-7 months old) male mice of FVB/N (genotype H-2q) and 129/Sv (genotype H-2b) strains were administered the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 30 mg/kg (control group), and after 7 days, hUC-MMSCs (500,000 cells) were transplanted into the tail vein. Behavioral reactions were assessed in open field, rigidity, and rotarod tests. The relative content of T-lymphocytes and activated macrophages in the brain was measured by flow cytometry, and the mass of lymphoid organs was determined. Results. Under the influence of MPTP, the number of rearings, "sniffs into the nest," body length, and step length decreased, the number of boluses increased in FVB/N and 129/Sv mice, and the number of squares crossed in the open field test decreased in 129/Sv mice. In the brain of mice from both lines, the content of activated macrophages increased, and in FVB/N mice, the number of T-lymphocytes also increased. The thymus mass decreased in mice from both lines, while the spleen mass decreased only in 129/Sv mice. The transplantation of hUC-MMSCs improved predominantly motor activity in FVB/N mice, while in 129/Sv mice, emotional activity improved, and manifestations of rigidity decreased in mice from both lines. The content of T-lymphocytes and activated macrophages in the brain of mice from both lines, as well as the thymus mass, corresponded to the values of intact animals. MMSC transplantation promoted the survival of FVB/N and 129/Sv mice with the MPTP-induced parkinsonism model. Conclusions. The manifestations of behavioral disorders, changes in the content of T-lymphocytes and activated macrophages in the brain, and the mass of lymphoid organs in mice with the MPTP-induced parkinsonism model, as well as the positive effects of transplanted hUC-MMSCs in these animals, largely depend on their genotype according to the H-2 system (analogous to the HLA system in humans). The results may provide a basis for developing personalized cell therapy for this pathology using multipotent mesenchymal stromal cells.

Multipotent mesenchymal stromal cells of various origins reduce reactive gliosis in the hippocampal CA1 area during acute ischemia-reperfusion of the rat brain

Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.

Mechanisms of antifibrotic action of placental multipotent mesenchymal stromal cells

The aim of the study was to investigate the mechanisms of action of multipotent mesenchymal stromal cells (MMSCs) in a model of tetrachloromethane-induced liver fibrosis in mice. The experiments were performed on 50 mice. MSCs isolated from mouse placenta choriona were used in the study. MSCs were transplanted at a dose of 1 million cells into the tail vein. α-SMA, MMP-9, MMP 13, and TIMP-1 positive regions were analyzed by immunohistochemical method to evaluate the mechanisms of MMSCs action. Sirius red dye was used for connective tissue staining. HGF and TGF-β were determined by immunoassay in liver homogenate. We obtained that transplantation of MMSCs leads to a decrease in the area of α-SMA, TIMP-1 positive regions, an increase in the number of cells expressing MMP-9 and MMP 13. An increase in the level of hepatocyte growth factor and a decrease in transforming growth factor beta in liver homogenate after hMSCs transplantation in liver fibrosis was found. The results of the study demonstrated the efficacy of placental MMSCs in liver fibrosis. The antifibrotic mechanisms of action of hMSCs can include the ability to increase the expression of HGF, decrease the level of TGF-β, increase the production of matrix metalloproteinases-9 and -13, as well as the ability to inhibit the expression of tissue inhibitor of matrix metalloproteinases type 1.

Concerns About Mesenchymal Stem Cell Therapy

Dear Editor, Multipotent mesenchymal stromal cells (MSCs), because of their potential for treating diseases, have gained considerable attention over the past 30 years for their immunosuppressive properties and tissue regeneration capabilities.1,2 This grew into an interest in the 1970s by Friedenstein and contemporaries after studying the bone m ar row.3 MSCs are an excellent candidate for cell therapy because of having intrinsic differentiation potentials into bone, cartilage and fat cells not found previously in other cells. They can also be isolated and expanded easily in vitro, and produce abundant useful growth factors and cytokines.2,4Mesenchymal stem cells have become the top used stem cell type for clinical application with encouraging results.5,6 Significant progress has been made in stem cell research in recent years. The main therapeutic effects of MSCs are now attributed to the stimulation of several innate repair processes in injured tissues in vivo by secreted factors as well as the immunomodulation response. Therefore, MSC therapy is expected to find clinical application in human diseases.6,7 However, there are some critical issues that need to be addressed before MSCs can be used for clinical therapy in humans which will help determine the efficiency of cells administered to the patients as a therapeutic approach, most important of which is immunosuppressive properties.8,9 MSCs can be affected by tumor support that may affect potential tumorigenesis after MSCs transplantation, including different donors and tissues, inconsistent protocols, varying dosages and differing transfusion patterns, and mechanisms that control the behavior of the MSCs at the target site.10,11 Because of their unique features, stem cells are undoubtedly a great hope for the treatment of many diseases. More research is developing on the potential long-term risks associated with MSC therapy. However, Additional studies would also be a major contribution to stem cell biology in general as well as their transplantation.

The effects of adipose-derived multipotent mesenchymal stromal cells transplantation on motor activity and function of the sciatic nerve in mice with peripheral neuropathy

The Charcot–Marie–Tooth disease type 1A (SHMT1A) is one of the most common hereditary motor-sensory peripheral neuropathies, which is caused by demyelination of motor and sensory nerve fibers and leads to nerve dysfunction. There are currently no effective treatments for hereditary neuropathies, but recent studies indicate a number of potentially effective therapeutic agents, including multipotent mesenchymal stromal cells (MMSCs). The aim of the study was to evaluate the effect of adipose-derived MMSCc transplantation on motor activity and sciatic nerve function of transgenic mice with peripheral neuropathy. Materials and methods. The transgenic B6.Cg-Tg(PMP22)C3Fbas/J mice with peripheral neuropathy were injected intramuscularly with MMSCs, which were isolated from the adipose tissue of FVB-Cg-Tg(GFPU) mice transgenic by GFP. Motor activity of experimental animals was investigated in dynamics after 2, 4, 6, 8 and 10 weeks using the behavioral balance beam test. The functions of the sciatic nerve were analyzed according to the footprint test by calculating the sciatic functional index (SFI). Results. For 2-10 weeks in animals with neuropathy, disease progression was observed, which was expressed in an increasing increase in the number of slidings of the hind limbs from the beam and the time required to walking the distance. SFI in animals of this group decreased and at the 10th week was -47.0 ± 2 units. In contrast, from the 2nd week of the experiment, mice with neuropathy after MMSCs transplantation performed 20 % fewer slidings and spent 11 % less time in the balance beam test compared to animals without cell transplantation. In the same period, an increase of SFI up to -30.2 ± 2 versus -34.6 ± 0.9 units was observed, respectively. At the 10th week after the injection of MMSC, the SFI value was -10.1 ± 2.3 units and correlated with a decrease in the number of slidings and the time spent on the balance beam test. Conclusions. MMSCs transplantation improves the sciatic functional index and fine motor skills in mice with peripheral neuropathy. MMSCs have the potential to be an effective therapeutic agent in the treatment of peripheral neuropathy at Charcot-Marie-Tooth disease.

Immediate results of intranasal administrations of multipotent mesenchymal stromal cells (MMSC) to Parkinson's disease (PD) patients

Introduction PD is a steadily progressive neurodegenerative disease. MMSC administration is considered one of the most promising therapies to modify the course of the disease. Objective Assessment of the immediate results of intranasal transplantation of autologous MMSC on motor symptoms of patients with PD. Materials and methods Four patients with PD were subjected to cell transplantation (all males; age = 42,7 ± 8,3 SD). Neurological examination was carried out in the morning after a 12 or (24) - hour break in taking anti-Parkinsonian drugs («OFF-state»), and one hour after the drugs were taken («ON-state»). The intensity of motor symptoms was assessed using the third part of the Unified Parkinson's disease Rating Scale (UPDRS) of the International Society for Movement Disorders. Initial assessment was performed 1 day before the transplantation, and the progress was measured one week after the procedure. Non-parametric methods of statistical analysis were used. The study was approved by local ethics committee. All subjects signed informed consent form before participating in the study. Results An improvement was detected in all the patients. Before the transplantation median levels of UPDRS in «OFF»-state was 33.4 [28.7; 39.2], and in «ON»-28.9 [21.2; 34.9]. After the procedure - «Off»-period was 31.1 [26.4; 36.5], «ON»-26.2 [19.4; 31.4]. Conclusion Transplantation of MMSC is a promising therapeutic intervention in treatment of PD that could influence the symptoms, and potentially the pathogenesis, of the disease. However, further examination is needed to estimate the consequences of this complex and insufficiently explored method.

Impact of the Transplantation of Multipotent Mesenchymal Stromal Cells after Liver Resection on Blood Biochemical Parameters in Mature and Old Laboratory Animals

The aim of this study was to study the effect of multipotent mesenchymal stromal cells (MMSC) transplantation on blood biochemical parameters after liver resection in Mature and old laboratory animals. The conducted studies show the ability of old laboratory animals to respond to MMSC transplantation after liver resection by reducing the severity of hepatocyte cytolysis. A comparative analysis of the biochemical parameters of Mature and old laboratory animals after liver resection should be noted a more pronounced response of mature animals in relation to the ability of the liver to synthesize urea.

Canine Adipose-Derived Mesenchymal Stromal Cells Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury

Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham (n = 8); Crush+PBS (n = 8); Crush+MSC (n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group (p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality (p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group (p < 0.04). There were no statistical differences in muscle weight between the groups (p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2–4 weeks in the rat model of sciatic nerve crush injury.

Effects of autologous gingiva-derived cells with myogenic potential on regeneration of skeletal muscle

In our recent studies we found for the first time the ability of human multipotent mesenchymal stromal cells (MSCs) derived from alveolar gingiva (alveolar mucosa) to differentiate into myogenic direction. The aim of the present study was to evaluate the effects of autologous gingiva-derived MSCs with myogenic potential on the regeneration of muscular tissue after mechanical damage. The study was conducted on 11 male rabbits. Biopsy of alveolar gingiva was performed at each animal before experiment for autologous MSCs obtainment. Cultures of MSCs were induced in vitro into myogenic direction. To model the damage, the medial heads of the gastrocnemius muscles were intersected on both pelvic limbs of the rabbit. Injection of autologous MSCs was performed on the seventh day after injury into the damaged muscle of one of the extremities, while equal volume of saline (control) was injected into the muscle of the contralateral limb. The animals were sacrificed on 0, 21, and 35 days after the administration of cells. MSCs transplantation led to significant reduction of the area of muscle damage. Immunohistochemical analysis revealed earlier increase in the proportion of MyoD- and myogenin-positive cells, as well as decrease in the expression of Ki-67 in damaged tissue, in experimental group compared to the control. Autologous cells did not significantly affect the composition of muscle fibers. Significant decrease in the proportion of fibrous tissue was also observed in the experimental group. The results indicate the effectiveness of autologous alveolar gingiva-derived MSCs for treatment of mechanical damage of muscle tissue. Local administration of cells accelerated reparative regeneration and prevented fibrosis.

Combination of the multipotent mesenchymal stromal cell transplantation with administration of temozolomide increases survival of rats with experimental glioblastoma.

Glioblastoma multiforme (GM) is an aggressive malignant tumor of the brain. The standard treatment of GM is surgical resection with consequent radio- and chemotherapy with temozolomide. The prognosis is unfavorable, with a survival time of 12-14 months. The phenomenon of targeted migration to the tumor in the brain opens novel possibilities for the treatment of GM. Multipotent mesenchymal stromal cells (MMSCs) are a cell type with anti-carcinogenic properties and can be used to optimize GM therapy. The aim of the present study was to investigate the effects of MMSC transplantation in the chemotherapy of a rat model of C6 glioma. A total of 130 animals were divided into a control group, a temozolomide group, MMSCs group and temozolomide + MMSCs group. The experiment was performed over 70 days, and a combination of molecular biology, surgical and neuroimaging techniques, as well as histological and physiological examinations was used. Tumor size was smallest in the temozolomide (115.76 ± 16.25 mm(3)) and in temozolomide + MMSCs (114.74 ± 5.54 mm(3)) groups, which was significantly smaller than the neoplastic node size in the control group (202.09 ± 39.72 mm(3)) (P<0.05). The animals in the temozolomide + MMSCs group showed significantly higher survival rates in comparison with those in the control and temozolomide groups. The MMSCs migrated from the site of implantation to the neoplastic focus and interacted with glioma cells; however, the mechanism requires further research. In conclusion, MMSC transplantation combined with temozolomide treatment significantly extended the survival of experimental animals in comparison with those treated with temozolomide only.

Effect of autologous mesenchymal pluripotent stem cells transplantation on liver microcirculation in rats with experimental liver cirrhosis

Aim. To study the effect of autologous bone marrow pluripotent stem cells transplantation on liver microcirculation in experimental model of liver cirrhosis.Methods. 43 white Wistar male rats with body weight of 150-180 g aged at least 3 months were used, in which autologous pluripotent mesenchymal stromal cells transplantation was performed. Considering the animals mortality at the cirrhosis modeling stage, which was 9.3% (4 out of 43 rats), the first group included 19 rats in which stromal cells were transplanted into the portal vein; in the second group (20 rats) the cells were injected into the common hepatic artery. Liver microcirculation was studied using laser Doppler flowmetry and wavelet analysis. Examinations were performed during the operation prior to autologous pluripotent mesenchymal stromal cells transplantation in rats with experimental liver cirrhosis, as well as on the 8th week of treatment.Results.In modeled liver cirrhosis, the microcirculation index was decreased by 24.5% (pConclusion. The repeated studies of microcirculation based on laser Doppler during the treatment of animals with experimental liver cirrhosis indicates the advantages of intra-arterial autologous multipotent mesenchymal stromal cells transplantation.

Intrahippocampal transplantation of mesenchymal stromal cells promotes neuroplasticity

Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus. Rat bone marrow-derived MSC were labeled with very small superparamagnetic iron oxide particles (VSOP), which allowed for non-invasive graft localization by magnetic resonance imaging (MRI). Moreover, MSC were transduced with lentiviral vectors to express the green fluorescent protein (GFP). The effects of bilateral MSC transplantation on hippocampal cellular plasticity were assessed using the thymidine analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU). Behavioral testing was performed to examine the consequences of intrahippocampal MSC transplantation on locomotion, learning and memory, and anxiety-like and depression-like behavior. We found that intrahippocampal transplantation of MSC resulted in enhanced neurogenesis despite short-term graft survival. In contrast, systemic administration of the selective serotonin re-uptake inhibitor citalopram increased cell survival but did not affect cell proliferation. Intrahippocampal transplantation of MSC did not impair behavioral functions in rats, but only citalopram exerted anti-depressant effects. This is the first study to examine the effects of intrahippocampal transplantation of allogeneic MSC on hippocampal structural plasticity and behavioral functions in rats combined with non-invasive cell tracking by MRI. We found that iron oxide nanoparticles can be used to detect transplanted MSC in the brain. Although graft survival was short, intrahippocampal transplantation of MSC resulted in long-term changes in hippocampal plasticity. Our results suggest that MSC can be used to stimulate adult neurogenesis.

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

Type 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential.Our preclinical results should be taken into account when designing phase II clinical trials aimed to evaluate MSC transplantation in patients with T1D. Cells should be isolated form healthy donor, insulin prophylaxis could be maintained and a second dose, after an elapse of two months, appears unnecessary in the medium-term.

Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury

Previous reports established that after a contusion injury to the rat spinal cord, locomotor function was enhanced by the transplantation of cells from bone marrow referred to as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). It has also been established that neural stem cells (NSCs) enhance locomotor function after transplantation into the injured rat spinal cord. However, the beneficial effects of NSCs are limited by graft-induced allodynia-like responses. Little is known about the effects of MSCs on sensory function in spinal cord injury. Therefore, the objective of this research was to determine whether transplantation of MSCs into the injured rat spinal cord induces allodynia-like responses. Contusion injuries of two different severities were induced in rats to examine the effects of transplantation with MSCs on sensorimotor deficits. The effects of MSCs on chronic inflammation were investigated, since inflammation is reported to have a role in the sensorimotor deficits associated with spinal cord injury. In addition, observations in other models suggest that MSCs possess immunosuppressive effects. We found that in contrast to previous observations with the transplantation of neural stem cells, transplantation of MSCs did not induce allodynia. MSCs attenuated injury-induced sensitivity to mechanical stimuli but had no effect on injury-induced sensitivity to cold stimuli. MSCs also significantly attenuated the chronic inflammatory response as assayed by GFAP immunoreactivity for reactive astrocytes and ED1 immunoreactivity for activated macrophages/microglia. In addition, transplantation of MSCs increased white matter volumes and decreased cyst size in sections of the cord containing the lesion. The results suggest that the sensorimotor enhancements produced by MSCs can at least in part be explained by anti-inflammatory/immunosuppressive effects of the cells, similar to such effects of these cells observed in other experimental models.

Comparative characterization of bone marrow-derived mesenchymal stromal cells from four different rat strains

Bone marrow (BM) multipotent mesenchymal stromal cells (MSC) hold great potential for cell-based regenerative medicine. Because of the growing use of autologous rat MSC transplantation in various rat models, there is a need to establish minimal criteria for rat MSC characterization independent of the specific strain employed in each study. We aimed to compare the phenotypic and functional traits of BM MSC from the four strains of rats commonly used in research: Fisher, Lewis, Sprague-Dawley and Wistar. Rat MSC were isolated from the BM of the four different rat strains in an identical fashion. Cells were characterized for their cell-surface phenotype in early and late passage. Functional mesenchymal differentiation capacities were examined following adipogenic and osteogenic inductions. Population doubling times were determined across the four strains throughout 10 passages. In vitro proliferation assays of immune cells were conducted following co-culture of spleen cells and MSC of the four different strains. We found that rat MSC from different strains exhibited similar cell-surface phenotype. Expansion rates and differentiation capacities of the MSC were also similar across the different strains. Co-culture of rat MSC with spleen cells obtained from rats of a different strain did not induce proliferation of immune cells. Our findings suggest that BM-derived MSC from different strains share similar characteristics, in contrast to the variations previously described in the characterization of mice MSC from different strains.

Systemic Administration of Multipotent Mesenchymal Stromal Cells Reverts Hyperglycemia and Prevents Nephropathy in Type 1 Diabetic Mice

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 × 10 6 MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.