Project description:We had analysed gene expression profile of brain in SCI rat by MSC. Compared with MSC intravenous and vehicle injection at SCI day3. We used Clariom D / Gene Chip® Rat Transcriptome Array (RTA 1.0., Affymetrix, Santa Clara, CA, USA).
Project description:Investigation of whole genome gene expression level changes in Inflammatory bowel disease rats after MSC transplantation, compared to IBD control rats, and to explore the mechanism of MSC transplantation. A four chip study using total RNA recovered from two separate IBD rats after MSC transplantation and two separate IBD control rats. Each chip measures the expression level of 26,419 genes from normal rat and IBD rat treated with MSC transplantation.
Project description:Investigation of whole genome gene expression level changes in Inflammatory bowel disease rats after MSC transplantation, compared to IBD control rats, and to explore the mechanism of MSC transplantation.
Project description:We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. 52 total samples were analyzed in 13 different groups. Each group include 4 samples and each one were analyzed as a biological replica. The intact animals were used as control of injury. The vehicle (VHC) groups were used as control of transplantation procedure. The MSC or OEC graft were injected at the day of injury (acute graft) or seven days after injury (delayed graft). The samples from engrafted animals were obtained at 2 or 7 days after cell transplantation. To determine the effects of MSC or OEC transplantation, the expression value of each engrafted sample were compared with correspondent VHC group.
Project description:We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.
Project description:The present study is intended to disclose the transcriptional profile of the temporal evolution through the different stages after SCI as well as the molecular processes underlying the NPC based-therapy in order to transcriptionally characterize its therapeutical mechanism. This transcriptional profile analysis of total RNA samples from spinal cord homogenates of adult rats (Sprague Dawley) provides tissular (tought not cell-type specific) information of the critical time points after the injury from 1 to 8 weeks (acute, sub-acute and early-chronic and late-chronic stages) which conferred a wide temporal coverage making it ideal for studying the temporal dynamics of SCI. Furthermore, we have evaluated the impact of intramedullary acute or subacute transplantation of NPCs over the transcriptional regulation of the spinal cord tissue in order to define the functional outcomes of the NPCs therapy.
Project description:Engraftment and differentiation of donor hematopoietic stem cells is decisive for the clinical success of allogeneic stem cell transplantation (alloSCT) and depends on the recipient’s bone marrow (BM) niche. Presumably, a damaged niche contributes to poor graft function post-alloSCT, but the underlying mechanisms and specifically the role of BM multipotent mesenchymal stroma cells (MSC) are ill defined. Upon multivariate analysis in a cohort of 732 individuals, we observed a reduced presence of proliferation-capable MSC in BM-aspirates from patients (N=196) who had undergone alloSCT (OR 0.61, p=.028). This was confirmed by paired analysis in 30 patients showing a higher frequency of samples with a lack of MSC presence post-alloSCT compared to pre-alloSCT. This reduced MSC presence was associated with reduced survival of patients following alloSCT and specifically with impaired graft function. Post-alloSCT MSC showed diminished in vitro proliferation along with a transcriptional antiproliferative signature, upregulation of epithelial-mesenchymal transition and extracellular matrix pathways and abnormal cytokine release in coculture with hematopoietic cells. In order to avoid in-vitro-culture bias we isolated the CD146+/CD45-/HLA-DR- BM cell fraction, which comprised the entire MSC population. The post-alloSCT isolated native CD146+MSC showed a similar reduction in proliferation capacity and shared the same antiproliferative transcriptomic signature as for post-alloSCT adherence-isolated MSC. Taken together, our data show that alloSCT confers damage to the proliferative capacity of native MSC, which is associated with reduced patient survival after alloSCT and impaired engraftment of allogeneic hematopoiesis. These data represent the basis to elucidate mechanisms of BM-niche reconstitution post-alloSCT and its therapeutic manipulation.
Project description:We conducted a time-course RNA-seq of spinal cord segments at the lesion site without or with hUC-MSC treatment at subacute phase of SCI to identify genes involved in hUC-MSC-mediated recovery
Project description:The number of elderly patients with spinal cord injury (SCI) is increasing worldwide, representing a serious burden for both the affected patients and the community. Previous studies have demonstrated that neural stem cell (NSC) transplantation is an effective treatment for SCI in young animals. Here we show that NSC transplantation is as effective in aged mice as it is in young mice, even though aged mice exhibit more severe neurological deficits after SCI. NSCs grafted into aged mice exhibited better survival than did those grafted into young mice. Furthermore, we show that the neurotrophic factor HGF plays a key role in the enhanced functional recovery after NSC transplantation observed in aged mice with SCI. The unexpected results of the present study suggest that NSC transplantation is a potential therapeutic modality for SCI, even in elderly patients.
Project description:Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the microenvironment that the cells encounter after administration may impact the properties of MSC. It has been demonstrated that the large majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the effect of freeze-thawing and of the mouse lung microenvironment on human adipose tissue-derived MSC. The effect of freeze-thawing on the whole genome expression profile of MSC was small and did not exceed inter-donor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells after blood exposure in vitro and after infusion to mice. Exposure for 2h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological and metabolic pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and that disease specific conditions may shape MSC after administration.