Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy

Cell therapy has emerged as a promising strategy for treating neurological diseases such as stroke, spinal cord injury, and various neurodegenerative diseases, but both embryonic neural stem cells and human induced Pluripotent Stem Cell- (iPSC-) derived neural stem cells have major limitations which restrict their broad use in these diseases. We want to find a one-step induction method to transdifferentiate the more easily accessible Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) into neural stem/progenitor cells suitable for cell therapy purposes. In this study, UC-MSCs were induced to form neurospheres under a serum-free suspension culture with Epidermal Growth Factor- (EGF-) and basic Fibroblast Growth Factor- (bFGF-) containing medium within 12 hours. These MSC-derived neurospheres can self-renew to form secondary neurospheres and can be readily induced to become neurons and glial cells. Real-time PCR showed significantly upregulated expression of multiple stemness and neurogenic genes after induction. RNA transcriptional profiling study showed that UC-MSC-derived neurospheres had a unique transcriptional profile of their own, with features of both UC-MSCs and neural stem cells. RayBio human growth factor cytokine array analysis showed significantly upregulated expression levels of multiple neurogenic and angiogenic growth factors, skewing toward a neural stem cell phenotype. Thus, we believe that these UC-MSC-derived neurospheres have amenable features of both MSCs and neural stem/progenitor cells and have great potential in future stem cell transplantation clinical trials targeting neurological disorders.

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Timing of Umbilical Cord Blood Derived Mesenchymal Stem Cells Transplantation Determines Therapeutic Efficacy in the Neonatal Hyperoxic Lung Injury

PLoS ONE ◽

10.1371/journal.pone.0052419 ◽

2013 ◽

Vol 8 (1) ◽

pp. e52419 ◽

Cited By ~ 81

Author(s):

Yun Sil Chang ◽

Soo Jin Choi ◽

So Yoon Ahn ◽

Dong Kyung Sung ◽

Se In Sung ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Therapeutic Efficacy ◽

Hyperoxic Lung Injury ◽

Stem Cells Transplantation

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Differentiation of Human Umbilical Cord Derived Mesenchymal Stem Cells Into Neural Stem Cells Induced by hPRDX5

10.21203/rs.3.rs-1061159/v1 ◽

2021 ◽

Author(s):

Yuanyuan Jin ◽

Beichen Shi ◽

Qiang Fan ◽

Kun Liu ◽

Shuai Fan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Neural Stem Cells ◽

Umbilical Cord ◽

Expression Profiles ◽

Antigen Expression ◽

Culture Method ◽

Human Umbilical Cord ◽

Differentiation Potential ◽

Surface Antigen Expression

Abstract Background: The objectives of this study were to investigate the characteristics and capacity of human umbilical cord‑derived mesenchymal stem cells (hUC-MSCs) differentiation into neural stem cells (NSCs) and whether this event enhanced by hPRDX5. Methods and Results: The adherent cells were obtained from umbilical cord of normal full-term newborn by caesarean section under aseptic condition, and cultivated by tissue block culture method. The surface antigen expression profiles of hUC-MSCs were monitored and the multi-directional differentiation potential was identified. Following amplification, the cells of the 4th passage were divided into 5 groups (groups A-E). The morphology was observed under inverted microscope, and the positive expression rate of markers of neural stem cell was detected by immunocytochemical and western blot. Flow cytometry revealed that the hUC-MSCs expressed CD29, CD73, CD90 and CD105, but not CD19, CD34, CD45 or HLA-DR. Treatment with hPRDX5 led to the surface markers of neural stem cells which were positive for Nestin, but negative for NSE and GFAP expression. Conclusions: Thus, the findings of the present study demonstrate that hPRDX5 effectively promotes hUC-MSCs to differentiate into neural stem cells possibly through TLR4 signaling pathway.

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Mesenchymal stem cells from human umbilical cord regulate the expression of major histocompatibility complex in human neural stem cells and their lineages

Neuroscience Letters ◽

10.1016/j.neulet.2020.135359 ◽

2020 ◽

Vol 738 ◽

pp. 135359

Author(s):

Hongna Yang ◽

Feng Wang ◽

Xiaodun Liu ◽

Hao Wang ◽

Tingyu Qu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Major Histocompatibility Complex ◽

Neural Stem Cells ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Major Histocompatibility ◽

Human Neural Stem Cells ◽

Histocompatibility Complex

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Co-Transplantation of Human Umbilical Cord Mesenchymal Stem Cells and Human Neural Stem Cells Improves the Outcome in Rats with Spinal Cord Injury

Cell Transplantation ◽

10.1177/0963689719844525 ◽

2019 ◽

Vol 28 (7) ◽

pp. 893-906 ◽

Cited By ~ 5

Author(s):

Lei Sun ◽

Fan Wang ◽

Heng Chen ◽

Dong Liu ◽

Tingyu Qu ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Neural Stem Cells ◽

Umbilical Cord ◽

Myelin Sheath ◽

Human Umbilical Cord ◽

Human Neural Stem Cells ◽

Cord Injury

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) are promising graft materials for cell therapies in spinal cord injury (SCI) models. Previous studies have demonstrated that MSCs can regulate the microenvironment of NSCs and promote their survival rate. Furthermore, several studies indicate that MSCs can reduce stem cell transplantation-linked tumor formation. To our knowledge, no previous studies have determined whether co-transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and human neural stem cells (hNSCs) could improve the outcome in rats with SCI. Therefore, we investigated whether the transplantation of hUC-MSCs combined with hNSCs through an intramedullary injection can improve the outcome of rats with SCI, and explored the underlying mechanisms. In this study, a moderate spinal cord contusion model was established in adult female Wistar rats using an NYU impactor. In total, 108 spinal cord-injured rats were randomly selected and divided into the following five groups: 1) hUC-MSCs group, 2) hNSCs group, 3) hUC-MSCs+hNSCs group, 4) PBS (control) group, and 5) a Sham group. Basso, Beattie and Bresnahan (BBB) behavioral test scores were used to evaluate the motor function of all animals before and after the SCI weekly through the 8th week. Two weeks after transplantation, some rats were sacrificed, immunofluorescence and immunohistochemistry were performed to evaluate the survival and differentiation of the transplanted stem cells, and brain-derived neurotrophic factor (BDNF) was detected by ELISA in the injured spinal cords. At the end of the experiment, we evaluated the remaining myelin sheath and anterior horn neurons in the injured spinal cords using Luxol Fast Blue (LFB) staining. Our results demonstrated that the surviving stem cells in the hUC-MSCs+hNSCs group were significantly increased compared with those in the hUC-MSCs alone and the hNSCs alone groups 2 weeks post-transplantation. Furthermore, the results of the BBB scores and the remaining myelin sheath evaluated via LFB staining in the injured spinal cords demonstrated that the most significantly improved outcome occurred in the hUC-MSCs+hNSCs group. The hUC-MSCs alone and the hNSCs alone groups also had a better outcome compared with that of the PBS-treated group. In conclusion, the present study demonstrates that local intramedullary subacute transplantation of hUC-MSCs, hNSCs, or hUC-MSCs+hNSCs significantly improves the outcome in an in vivo moderate contusion SCI model, and that co-transplantation of hUC-MSCs and hNSCs displayed the best outcome in our experiment.

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Effects of Intravitreal Injection of Hypoxia-Induced Umbilical Cord Mesenchymal Stem Cell Exosomes On Diabetic Retinopathy

10.21203/rs.3.rs-994654/v1 ◽

2021 ◽

Author(s):

Yan Fu ◽

Zhao-Hui Gu ◽

Yue-Ling Zhang ◽

Xiao-Ying Wen ◽

Na Yang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Retinopathy ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Intravitreal Injection ◽

Umbilical Cord ◽

Diabetic Rats ◽

Human Umbilical Cord ◽

Retinal Microvasculature

Abstract Diabetic retinopathy (DR) is a highly specific condition affecting the microvasculature that is the leading cause of visual impairment in working-age people in developed countries. The ability of intravitreal administration of mesenchymal stem cells (MSCs) to repair the retinal vasculature and neurons of the inner retina in DR has been explored. It was recently revealed that exosomes are primarily responsible for the therapeutic effects of MSCs; therefore, intravitreal injection of these vesicles appears to be a better option for treatment of retinal injury, and there is evidence that hypoxic conditions can promote exosome release from MSCs. Here we investigated the effect of intravitreal injection of hypoxia-induced human umbilical cord mesenchymal stem cell exosomes (hypo-hucMSC-Exs) on the retinal microvasculature in rats with DR. We also assessed whether hypo-hucMSC-Exs exhibited greater effects on DR than exosomes from human umbilical cord mesenchymal stem cells not exposed to hypoxia (hucMSC-Exs). Exosomes were isolated from MSCs cultured under normoxic and hypoxic culture conditions. Transmission electron microscope, nanoparticle tracking, and western blot analyses were applied to characterize hucMSC-Exs. Streptozotocin (STZ)-induced diabetic rats were used as a model for DR. Fundus fluorescein angiography (FFA) was conducted to evaluate retinal microvasculature changes in vivo at 4, 8, and 12 weeks following intravitreal injection of exosomes. No significant changes were observed in the control rats without DR receiving intravitreal phosphate-buffered saline (PBS) injection throughout the study. Control model rats receiving PBS injections developed DR characterized by retinal microvascular changes, including tortuous vessels, massive microaneurysms, and late leakage of fluorescein dye was, which were visualized using FFA. These changes were ameliorated in diabetic rats treated with hucMSC-Exs. Further, injection of hypo-hucMSC-Exs remarkably reduced the extent of microvasculature lesions compared with hucMSC-Exs. These findings suggest that intravitreal injection of hucMSC-Exs can prevent diabetes-induced microvasculature lesions and that hypo-hucMSC-Exs can enhance this effect and have potential for application in DR prevention and treatment.

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