Published online Jul 26, 2023. doi: 10.4252/wjsc.v15.i7.713
Peer-review started: March 15, 2023
First decision: April 13, 2023
Revised: May 15, 2023
Accepted: June 26, 2023
Article in press: June 26, 2023
Published online: July 26, 2023
Processing time: 130 Days and 2.3 Hours
Based on the extensive skin integrity defects caused by burns, scalds, vasculopathy triggered skin ulcers, pressure ulcers, diabetic ulcerated feet, and so on, which are caused by the action of internal and external factors, the wounds develop pathological inflammatory reactions, which cannot achieve the healing through normal repair procedures, and then lead to slow or non-healing, causing severe disability or death to the patient, and at the same time, bringing a heavy economic burden to the patient's family. Studies have shown that impaired keratinocyte (KC) migration causes non healing wounds and is an important cause of chronic wound formation, whereas inhibition of their proliferation and differentiation functions does not result in the formation of non-healing wounds. Deriving the replacement cells from human-induced pluripotent stem cells (hiPSCs) allows for sufficient scale up and by using hiPSCs as the choice of human pluripotent stem cells (hPSC) will ensure immunocompatibility.
The specific mechanism of hiPSCs involvement in burn repair has not been fully revealed.
The current study showed that hiPSCs can effectively differentiate into KCs under the effect of inducers, but its effect on skin burn healing has not been reported. Therefore, this study was intended to observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice, and to preliminarily reveal the related mechanisms by which it exerts its effects.
In this study, we used the cell induced differentiation technique of hiPSCs to successfully differentiate hiPSCs cells into KCs (hiPSCs-KCs) using inducing factors. Subsequently, a murine skin-deep degree II burn model was constructed, and KCs induced to differentiate successfully were injected around the mouse skin wound, to deeply investigate the effect of transplantation of KCs induced to differentiate formed on the healing of murine skin wounds. In addition, a bioinformatics approach was taken to further explore the possible mechanism of hiPSCs-KCs transplantation involvement in wound healing.
The above results indicate that COL7A1 plays a role in accelerating wound healing by inhibiting the inflammatory response and promoting KC proliferation and migration in deep second-degree burn wounds. Therefore, it can be suggested that COL7A1 is vital for encouraging wound healing and providing a new target for deep second-degree burn wound treatment. However, there are a few limitations to our findings. For instance, we used FTY720 injection alone to suppress immune rejection in mice, based on previous experiments in the literature. FTY720 is a newly developed immunosuppressant that selectively reduces peripheral circulating lymphocytes and significantly prolongs the survival of transplanted organs in experimental animals. A study reported an increase in the number of T lymphocytes in mesenteric lymph nodes and a reduction within the spleen among FTY720-treated mice. Besides, FTY720 has been shown to promote local wound healing via an immunomodulatory mechanism after being delivered using a biomaterial. We hypothesized that local delivery of FTY720 can promote local wound healing through immunomodulatory mechanisms, which may also prevent delayed tissue repair after injury. Unfortunately, a control group without FTY720 injection was not considered in this investigation, so it was not possible to determine whether FTY720 could have an impact over tissue repair. Nevertheless, according to our findings, no immune rejection events were observed in our included mice, and the wound healing rate was within the normal range. Besides, future studies from our team will concentrate on modifying the experiment to account for FTY720's impact on tissue repair delay.
The above results indicate that COL7A1 can play a role in accelerating wound healing by inhibiting the inflammatory response and promoting KC proliferation and migration in deep second degree burn wounds, revealing the mechanism of COL7A1 for encouraging wound healing and providing a new target for deep second degree burn wound treatment.
This study will focus on the aspects of autologous transplantation of human iPSCs in the future.