scholarly journals Insight into Reepithelialization: How Do Mesenchymal Stem Cells Perform?

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Deyun Chen ◽  
Haojie Hao ◽  
Xiaobing Fu ◽  
Weidong Han

Wound reepithelialization is a cooperative multifactorial process dominated by keratinocyte migration, proliferation, and differentiation that restores the intact epidermal barrier to prevent infection and excessive moisture loss. However, in wounds that exhibit impaired wound healing, such as chronic nonhealing wounds or hypertrophic scars, the reepithelialization process has failed. Thus, it is necessary to explore a suitable way to mitigate these abnormalities to promote reepithelialization and achieve wound healing. Mesenchymal stem cells (MSCs) have the capacity for self-renewal as well as potential multipotency. These cells play important roles in many biological processes, including anti-inflammation, cell migration, proliferation, and differentiation, and signal pathway activation or inhibition. The mechanism of the involvement of MSCs in reepithelialization is still not fully understood. An abundance of evidence has shown that MSCs participate in reepithelialization by inhibiting excessive inflammatory responses, secreting important factors, differentiating into multiple skin cell types, and recruiting other host cells. This review describes the evidence for the roles that MSCs appear to play in the reepithelialization process.

2020 ◽  
Author(s):  
Tiechao Jiang ◽  
Zhongyu Wang ◽  
Ji Sun

Abstract Background: Cutaneous wound healing represents a morphogenetic response to injury, and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) is a promising source for cell-free therapy and skin regeneration. Methods: In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSCs-Ex on cutaneous wound healing in rats. In vitro studies , w e evaluated the role of hBM-MSCs-Ex in the two type s of skin cell s : human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation . For in vivo studies , we used a full-thickness skin wound model to evaluate the effects of hBM-MSCs-Ex on cutaneous wound healing in vivo . Results: The results demonstrated that hBM-MSCs-Ex promote both two type s of skin cell s growth effectively and accelerate the cutaneous wound healing. Interestingly , we found that hBM-MSCs-Ex significantly down-regulated TGF-β1, Smad2, Smad3, and Smad4 expression, while up-regulated TGF-β3 and Smad7 expression in the TGF-β/Smad signaling pathway . Conclusions: Our findings indicated that hBM-MSCs-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway . The current result s providing a new sight for the therapeutic strategy for the treatment of cutaneous wounds.


2020 ◽  
Vol 9 (7) ◽  
pp. 2161 ◽  
Author(s):  
Lucy V Trevor ◽  
Kirsten Riches-Suman ◽  
Ajay L Mahajan ◽  
M Julie Thornton

Interest in adipose tissue is fast becoming a focus of research after many years of being considered as a simple connective tissue. It is becoming increasingly apparent that adipose tissue contains a number of diverse cell types, including adipose-derived stem cells (ASCs) with the potential to differentiate into a number of cell lineages, and thus has significant potential for developing therapies for regenerative medicine. Currently, there is no gold standard treatment for scars and impaired wound healing continues to be a challenge faced by clinicians worldwide. This review describes the current understanding of the origin, different types, anatomical location, and genetics of adipose tissue before discussing the properties of ASCs and their promising applications for tissue engineering, scarring, and wound healing.


2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Yi Wang ◽  
Youguo Ying ◽  
Xiaoyan Cui

Mesenchymal stem cells (MSCs) are multipotential cells with capability to form coloniesin vitroand differentiate into distinctive end-stage cell types. Although MSCs secrete many cytokines, the efficacy can be improved through combination with neurotrophic factors (NTFs). Moreover, MSCs are excellent opportunities for local delivery of NTFs into injured tissues. The aim of this present study is to evaluate the effects of overexpressing NTFs on proliferation and differentiation of human umbilical cord-derived mesenchymal stem cells (HUMSCs). Overexpressing NTFs had no effect on cell proliferation. Overexpressing NT-3, BDNF, and NGF also had no significant effect on the differentiation of HUMSCs. Overexpressing NTFs all promoted the neurite outgrowth of embryonic chick E9 dorsal root ganglion (DRG). The gene expression profiles of the control and NT-3- and BDNF-modified HUMSCs were compared using RNA sequencing and biological processes and activities were revealed. This study provides novel information about the effects of overexpressing NTFs on HUMSCs and insight into the choice of optimal NTFs for combined cell and gene therapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Takahiro Teshima ◽  
Akito Matsuoka ◽  
Maika Shiba ◽  
Kazuho Dairaku ◽  
Hirotaka Matsumoto ◽  
...  

Adipose-derived mesenchymal stem cells (ADSCs) have been suggested their benefits in regenerative medicine for various diseases. Lipomas, benign neoplasms in adipose tissue, have been reported as a potential source of stem cells. These lipoma-derived mesenchymal stem cells (LDSCs) may be useful for regenerative medicine. However, the detailed characteristics of LDSCs have not been fully elucidated. This study investigated the cellular proteomics and secretomes of canine LDSCs in addition to morphology and proliferation and differentiation capacities. Some LDSCs isolated from canine subcutaneous lipomas were morphologically different from ADSCs and showed a rounded shape instead of fibroblast-like morphology. The phenotype of cell surface markers in LDSCs was similar to those in ADSCs, but CD29 and CD90 stem cell markers were more highly expressed compared with those of ADSCs. LDSCs had noticeably high proliferation ability, but no significant differences were observed compared with ADSCs. In regard to differentiation capacity compared to ADSCs, LDSCs showed higher adipogenesis, but no differences were observed with osteogenesis. Cellular proteomic analysis using two-dimensional gel electrophoresis revealed that over 95% of protein spots showed similar expression levels between LDSCs and ADSCs. Secretome analysis was performed using iTRAQ and quantitative cytokine arrays. Over 1900 proteins were detected in conditioned medium (CM) of LDSCs and ADSCs, and 94.0% of detected proteins showed similar expression levels between CM of both cell types. Results from cytokine arrays including 20 cytokines showed no significant differences between CM of LDSCs and that of ADSCs. Our results indicate that canine LDSCs had variability in characteristics among individuals in contrast with those of ADSCs. Cellular proteomics and secretomes were similar in both LDSCs and ADSCs. These findings suggest that LDSCs may be suitable for application in regenerative medicine.


2020 ◽  
Vol 143 (3) ◽  
Author(s):  
Rukmani Sridharan ◽  
Daniel J. Kelly ◽  
Fergal J. O'Brien

Abstract Upon implantation of a biomaterial, mesenchymal stem cells (MSCs) and macrophages contribute to the wound healing response and the regeneration cascade. Although biomaterial properties are known to direct MSC differentiation and macrophage polarization, the role of biomaterial cues, specifically stiffness, in directing the crosstalk between the two cell types is still poorly understood. This study aimed to elucidate the role of substrate stiffness in modulating the immunomodulatory properties of MSCs and to shed light on their complex interactions with macrophages when presented with diverse biomaterial stiffness cues, a situation analogous to the implant environment where multiple cell types interact with an implanted biomaterial to determine regenerative outcomes. We show that MSCs do not play an immunomodulatory role in the absence of an inflammatory stimulus. Using collagen-coated polyacrylamide gels of varying stiffness values, we demonstrate that the immunomodulatory capability of MSCs in the presence of an inflammatory stimulus is not dependent on the stiffness of the underlying substrate. Moreover, using paracrine and direct contact culture models, we show that a bidirectional crosstalk between MSCs and macrophages is necessary for promoting anti-inflammatory responses and positive immunomodulation, which is dependent on the stiffness of the underlying substrate. We finally show that direct cell–cell contact is not essential for this effect, with paracrine interactions promoting immunomodulatory interactions between MSCs and macrophages. Together, these results demonstrate that biophysical cues such as stiffness that are presented by biomaterials can be tuned to promote positive interactions between MSCs and macrophages which can in turn direct the downstream regenerative response.


Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 89
Author(s):  
Gi Cheol Park ◽  
Hyung-Sik Kim ◽  
Hee-Young Park ◽  
Yoojin Seo ◽  
Ji Min Kim ◽  
...  

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGβ1) expression, while total ITGβ1 expression was not affected. Inhibition of ITGβ1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGβ1 expression.


Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4197-4205 ◽  
Author(s):  
Keishi Otsu ◽  
Shonit Das ◽  
Sandra D. Houser ◽  
Sadiqa K. Quadri ◽  
Sunita Bhattacharya ◽  
...  

Abstract Mesenchymal stem cells (MSCs), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSCs and host cells, in particular endothelial cells (ECs), remain unclear. We show here in a matrigel angiogenesis assay that MSCs are capable of inhibiting capillary growth. After addition of MSCs to EC-derived capillaries in matrigel at EC:MSC ratio of 1:1, MSCs migrated toward the capillaries, intercalated between ECs, established Cx43-based intercellular gap junctional communication (GJC) with ECs, and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSCs are potentially cytotoxic and that when injected locally in tumor tissue they might be effective antiangiogenesis agents suitable for cancer therapy.


2020 ◽  
Author(s):  
Tiechao Jiang ◽  
Zhongyu Wang ◽  
Ji Sun

Abstract Background: Cutaneous wound healing represents a morphogenetic response to injury, and it designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) is a promising source for cell-free therapy and skin regeneration. Methods: In this study, we investigated the therapeutic effects and underlying mechanism of hBM-MSCs-Ex on cutaneous wound healing in rats. We assessment of the role of hBM-MSCs-Ex in the two type of skin cell: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). proliferation in vitro . Furthermore, we used a full-thickness skin wounds to evaluate the effects of hBM-MSCs-Ex on cutaneous wound healing in vivo. Results: Our results demonstrated that hBM-MSCs-Ex promote both two type of skin cell growth effectively and accelerate the cutaneous wound healing ( p <0.01). Then, we found that hBM-MSCs-Ex significantly down-regulated TGF-β1, Smad2, Smad3, and Smad4 expression, while up-regulated TGF-β3 and Smad7 expression ( p <0.05). Conclusions: In conclusion, our findings indicated that hBM-MSCs-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway, providing a new sight for the therapeutic strategy of hBM-MSCs-Ex for the treatment of cutaneous wounds.


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