Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis

Liang, Xiaoting; Lin, Fang‐Yue; Ding, Yue; Zhang, Yuelin; Li, Mimi; Zhou, Xiaohui; Meng, Qingshu; Ma, Xiumei; Lu, Wei; Fan, Huimin; Liu, Zhongmin

doi:10.1186/s13287-021-02366-x

Cited by 37 publications

(29 citation statements)

References 45 publications

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“…The reduced angiogenic ability contributes to impaired wound healing and therefore pro-angiogenic therapy is highly desirable. It was shown that topical application of conditioned medium from induced pluripotent stem cells [39] or hydrogel-mediated delivery of umbilical cord blood-derived MSC [36] accelerates wound healing through enhanced angiogenesis. Our results clearly show that the supplementation of hydrogel with HATMSCs supernatant improves the tube formation process in angiogenic test in vitro.…”

Section: Discussionmentioning

confidence: 99%

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

Kraskiewicz

Hinc

Krawczenko

et al. 2021

IJMS

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Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to the translation of cell therapy into clinical use such as efficacy, safety and cost, we propose a hydrogel loaded with a secretome from the recently established human adipose tissue mesenchymal stem cell line (HATMSC2) as a potential treatment for chronic wounds. Biocompatibility and biological activity of hydrogel-released HATMSC2 supernatant were investigated in vitro by assessing the proliferation and metabolic activity of human fibroblast, endothelial cells and keratinocytes. Hydrogel degradation was measured using hydroxyproline assay while protein released from the hydrogel was assessed by interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) ELISAs. Pro-angiogenic activity of the developed treatment was assessed by tube formation assay while the presence of pro-angiogenic miRNAs in the HATMSC2 supernatant was investigated using real-time RT-PCR. The results demonstrated that the therapeutic effect of the HATMSC2-produced factors is maintained following incorporation into collagen hydrogel as confirmed by increased proliferation of skin-origin cells and improved angiogenic properties of endothelial cells. In addition, HATMSC2 supernatant revealed antimicrobial activity, and which therefore, in combination with the hydrogel has a potential to be used as advanced wound-healing dressing.

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Section: Discussionmentioning

confidence: 99%

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

Kraskiewicz

Hinc

Krawczenko

et al. 2021

IJMS

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“…hiPSC-MSCs showed better proliferation, survival, immunomodulatory properties, and therapeutic efficacy for myocardial repair than BM-MSC and possessed the capacity to transfer mitochondria to rescue mitochondrial dysfunction [ 6 , 48 ]. In accordance with their findings, our group showed that conditioned medium of hiPSC-MSC (iMSC-CdM) was superior to that derived from umbilical cord MSC in accelerating wound closure [ 45 ]. GMP-grade hiPSC-MSCs have been applied in acute steroid-resistant graft versus host disease (GVHD) in clinical trials [ 49 ].…”

Section: Discussionmentioning

confidence: 53%

“…We also found that Apelin-13 pretreatment greatly enhanced the angiogenic capacity of MSCs, as evidenced by the increased capillary-like tube formation of HUVECs cultured with conditioned medium and enhanced capillary and arteriole density in the ischemic heart tissue. Our previous studies have documented that the ERK signaling pathway is involved in regulating the angiogenic capacity of MSCs [ 25 , 45 ]. In this study, we also observed that inhibition of the ERK signaling pathway with U0126 significantly downregulated the angiogenic capacity of Apelin-13-treated MSCs, indicating that Apelin-13 stimulates the angiogenic capacity of MSCs by activating the ERK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival

Chen

Liang

Han

et al. 2022

Stem Cells International

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Although mesenchymal stem cell- (MSC-) based therapy has shown promising results for myocardial infarction (MI), low cell survival heavily limits its beneficial effects. Apelin plays an essential regulatory role in cell proliferation. This study was aimed at determining whether Apelin-13 pretreatment could improve the survival of MSCs in the ischemic heart and enhance their cardioprotective efficacy against MI. MSCs were pretreated with or without Apelin-13 for 24 hours and then exposed to serum deprivation and hypoxia (SD/H) for 48 hours. The mitochondrial morphology of MSCs was assessed by MitoTracker staining. The apoptosis of MSCs was determined by TUNEL staining. The level of mitochondrial reactive oxygen species (ROS) of MSCs was detected by Mito-Sox staining. MSCs and Apelin-13-pretreated MSCs were transplanted into the peri-infarct region in a mouse MI model. Apelin-13 pretreatment protected MSCs against SD/H-induced mitochondrial fragmentation and apoptosis. Apelin-13 pretreatment reduced ROS generation induced by SD/H in MSCs. Furthermore, Apelin-13 pretreatment enhanced the angiogenesis of MSCs under SD/H conditions. Mechanistically, Apelin-13 pretreatment inhibited SD/H-induced MSC apoptosis by downregulating mitochondrial fission via activation of the ERK pathway, and these effects were partially abrogated by ERK inhibitor U0126. Apelin-13 pretreatment promoted the survival of MSCs in the ischemic heart. Moreover, transplantation with Apelin-13-pretreated MSCs improved heart function and increased angiogenesis accompanied by decreased fibrosis compared with MSC transplantation at 28 days following MI. These findings reveal that pretreatment with Apelin-13 improves MSCs survival and enhances their therapeutic efficacy for MI. Our study provides a novel approach to improve MSC-based therapy for cardiovascular disease.

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“…Moreover, it has been well demonstrated that conditioned medium from iPSC‐derived MSCs has multiple impacts in the healing of full‐thickness excisional wounds as compared with umbilical cord‐derived MSCs. Indeed, they stated that this conditioned medium could stimulate HUVEC proliferation, tube formation, and energy metabolism via the ERK pathway 65 . According to the literature, it is clear that there is an outstanding opportunity for utilising iPSCs for skin wound healing applications by promoting angiogenesis.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

“…Indeed, they stated that this conditioned medium could stimulate HUVEC proliferation, tube formation, and energy metabolism via the ERK pathway. 65 According to the literature, it is clear that there is an outstanding opportunity for utilising iPSCs for skin wound healing applications by promoting angiogenesis. .…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing

Azari

Nazarnezhad

Webster

et al. 2022

Wound Repair Regeneration

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The timely management of skin wounds has been an unmet clinical need for centuries.While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell-based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo-derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro-angiogenic exosomes.Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro-angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro-angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing.As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro-angiogenic stem cells for treating acute and chronic skin wounds.

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Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis

Cited by 37 publications

References 45 publications

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival

Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing

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