This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM).

Mesenchymal stem cell-based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta-derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation-induced murine limb ischemia model was generated with fluorescent dye (CM-DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia-induced injury to mouse hind limbs by enhancement of angiogenesis.

Myocardial infarction (MI) is one of the higher mortality rates, and current treatment can only delay the progression of the disease. Experiments have shown that cell therapy could improve cardiac function and mesenchymal stem cells (MSCs)-based therapies provide a great promising approach in the treatment of MI. However, low cell survival and engraftment restricts the successful application of MSCs for treating MI. Here, we explored whether co-transplantation of a chitosan (CS) thermosensitive hydrogel with bone marrow-derived MSCs (BMSCs) could optimize and maximize the therapeutic of BMSCs in a mouse model of MI. The fate of transplanted BMSCs was monitored by bioluminescence imaging, and the recovery of cardiac function was detected by echocardiogram. Our results proved that CS hydrogel enhanced the BMSCs' survival and the recovery of cardiac function by protecting the vascular endothelial cells. Further studies revealed that the increased number of vascular endothelial cells was due to the fact that transplanted BMSCs inhibited the inflammatory response and alleviated the pyroptosis of vascular endothelial cells. In conclusions, CS hydrogel improved the engraftment of transplanted BMSCs, ameliorated inflammatory responses, and further promoted functional recovery of heart by alleviating vascular endothelial cell pyroptosis.

The mortality rate of post-hepatectomy liver failure (PHLF) remains very high, and liver transplantation is the only effective treatment regimen for PHLF. Cell transplantation is a potential treatment for liver diseases. Previous studies have proved that mesenchymal stem cells (MSCs) have immunomodulatory functions. In the present study, we found that MSCs promoted glycogen synthesis and liver regeneration in the treatment of PHLF. MSC transplantation also improved the survival rate of rats after 90% partial hepatectomy (PH). In our current study, we aimed to determine the efficacy and mechanism of MSC transplantation in the treatment of PHLF.

Mesenchymal stromal cells (MSCs) transplantation could enhance bone repair. However, the cell fate of transplanted MSCs, in terms of their local distribution and spatial associations with other types of cells were poorly understood. Here, we developed a single-cell 3D spatial correlation (sc3DSC) method to track transplanted MSCs based on deep tissue microscopy of fluorescent nanoparticles (fNPs) and immunofluorescence of key proteins. Locally delivered fNP-labeled MSCs enhanced tibial defect repair, increased the number of stem cells and vascular maturity in mice. fNP-MSCs persisted in the defect throughout repair. But only a small portion of transplanted cells underwent osteogenic differentiation (OSX+); a significant portion has maintained their expression of mesenchymal stem cell and skeletal stem cell markers (SCA-1 and PRRX1). Our results contribute to the optimization of MSC-based therapies. The sc3DSC method may be useful in studying cell-based therapies for the regeneration of other tissue types or disease models.

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83 ± 227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.

Long noncoding RNAs (lncRNAs) have been discovered to play a key role in adipogenesis, while the role of lncRNA human leukocyte antigen complex group 11 (HCG11) in adipocyte differentiation has not been studied clearly. We used human adipose-derived mesenchymal stem cells (hAdMSCs) to establish a model of cell differentiation in vitro and found that expression of lncRNA HCG11 was decreased during adipogenesis through real-time quantitative polymerase chain reaction analysis. Then, hAdMSCs were transfected with pcDNA-HCG11 or HCG11-shRNA (sh-HCG11); the adipogenic marker proteins were detected by Western blot, and the activity of lipogenesis enzymes was detected by spectrophotometry. The expression of CCAAT-enhancer-binding protein α, fatty acid-binding protein, peroxisome proliferator-activated receptor gamma 2 and the levels of acetyl coenzyme A carboxylase and fatty acid synthase FAS were significantly downregulated in hAdMSCs at different stages transfected with pcDNA-HCG11, while knockdown of lncRNA HCG11 promoted adipocyte differentiation. Bioinformatic analysis indicated that miR-204-5p was a potential target gene of HCG11, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. In addition, miR-204-5p directly targeting the 3'-untranslated region of SIRT1 was also predicted by StarBase and verified by luciferase reporter gene analysis. Enforced expression of miR-204-5p negatively regulated the SIRT1 protein level. Furthermore, SIRT1 overexpression significantly inhibited adipogenic marker protein, levels of lipogenesis enzymes, and the proliferation of hAdMSCs. When pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that the miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Taken together, we found that HCG11 negatively regulated cell proliferation and adipogenesis by the miR-204-5p/SIRT1 axis. Our findings might provide a new target for the study of adipogenesis in hAdMSCs and obesity.

The healing of tendon-bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs-PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs-PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs-PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon-bone interface. The biomechanical analysis showed that BMSCs-PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon-bone healing in the rabbit rotator cuff repair model.

Meniscus reconstruction is in great need for orthopedic surgeons. Meniscal fibrochondrocytes transplantation was proposed to regenerate functional meniscus, with limited donor supply. We hypothesized that coculture of synovial mesenchymal stem cells (SSC) with meniscal fibrochondrocytes (me-CH) can support matrix production of me-CH, thus reducing the number of me-CH needed for meniscus reconstruction. A pellet coculture system of human SSC and me-CH was used in this study. Enhanced glycosaminoglycans (GAG) in coculture pellets were demonstrated by Alcian blue staining and GAG quantification, when compared to monoculture. More collagen synthesis was shown in coculture pellets by hydroxyproline assay. Increased proliferation of me-CH was observed in coculture. Data from BrdU staining and ELISA demonstrated that conditioned medium of SSCs enhanced the proliferation and collagen synthesis of me-CH, and this effect was blocked by neutralizing antibody against fibroblast growth factor 1 (FGF1). Western blot showed that conditioned medium of SSCs can activate mitogen-activated protein kinase (MAPK) signaling pathways by increasing the phosphorylation of mitogen-activated regulated protein kinase 1/2 (MEK) and extracellular-signal-regulated kinases 1/2 (ERK). Overall, this study provided evidence that synovial MSCs can support proliferation and collagen synthesis of fibrochondrocytes, by secreting FGF1. Coimplantation of SSC and me-CH could be a useful strategy for reconstructing meniscus.

Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.

In comparing placental transfusion strategies, blood obtained from an umbilical cord that has been "milked" vs one in which clamping was simply delayed contains mesenchymal stromal cells in addition to solely hematopoietic stem cells, a composition more favorable for hematopoiesis, as suggested by its superior rescue of lethally irradiated bone marrow-depleted mice.

Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction (MI). However, the low retention of cells and drugs limits their therapeutic efficacies. Here, we propose a prefixed sponge carpet strategy, that is, aldehyde-dextran sponge (ODS) loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol (HP-β-CD@Res) is first bonded to the rat's heart via capillary removal of interfacial water from the tissue surface, and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue. Then, an aqueous biocompatible hydrazided hyaluronic acid (HHA) solution encapsulating mesenchymal stem cells (MSCs) is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction, thus prolonging the in vivo retention time of therapeutic drug and cells. Importantly, the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface, avoiding adhesion to other tissues. The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment, reduce cardiomyocyte apoptosis, and enhance the survival of transplanted MSCs, thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.