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Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
Published on: March 3, 2023
[Research advances on the targeted programmed cell death regulatory network for treatment of refractory diabetic
1Institute of Burn Research, State Key Laboratory of Trauma and Chemical Poisoning, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing Key Laboratory for Wound Repair and Tissue Regeneration, Chongqing 400038, China.
Abstract:
Refractory diabetic wounds are severe complications of diabetes mellitus, for which conventional treatments yield limited efficacy. Recent studies have demonstrated that the core pathogenesis lies in the dysregulation of the programmed cell death regulatory network induced by the hyperglycemic microenvironment. Specifically, excessive activation of lytic cell death such as necroptosis, ferroptosis, and pyroptosis drives persistent inflammation; while impairment of non-lytic cell death including apoptosis and cytoprotective autophagy as well as efferocytosis dysfunction results in impaired initiation of the inflammation resolution program. Distinct cell death pathways form a dynamic network through shared regulatory hubs and downstream signaling crosstalk, ultimately locking the wound in a vicious cycle of "cell death-inflammation-repair impairment". This review systematically elaborates on the dysregulation characteristics and interaction mechanisms of the programmed cell death regulatory network in diabetic wounds, and discusses the application prospects of combination therapies and precision stratified treatment.
Insights
Refractory diabetic wounds involve complex cell death pathway dysregulation. Targeting this programmed cell death network offers new therapeutic strategies for healing these chronic wounds.
Area of Science:
- Biomedical Science
- Wound Healing Research
- Cell Death Biology
Background:
- Refractory diabetic wounds are a significant clinical challenge with limited treatment options.
- Hyperglycemia in diabetes mellitus disrupts the programmed cell death regulatory network.
- This disruption leads to persistent inflammation and impaired wound repair.
Purpose of the Study:
- To systematically review the dysregulation of programmed cell death pathways in diabetic wounds.
- To elucidate the interaction mechanisms within the cell death regulatory network.
- To discuss novel therapeutic strategies for refractory diabetic wounds.
Main Methods:
- Literature review of recent studies on programmed cell death in diabetic wounds.
- Analysis of the interplay between lytic and non-lytic cell death pathways.
- Examination of efferocytosis dysfunction and its role in inflammation resolution.
Main Results:
- Excessive lytic cell death (necroptosis, ferroptosis, pyroptosis) promotes inflammation.
- Impaired non-lytic cell death (apoptosis, autophagy) and efferocytosis hinder inflammation resolution.
- A complex network of shared regulatory hubs and signaling crosstalk perpetuates a "cell death-inflammation-repair impairment" cycle.
Conclusions:
- Dysregulation of the programmed cell death network is central to refractory diabetic wound pathogenesis.
- Targeting this network, potentially through combination therapies and precision medicine, holds promise for improved treatment outcomes.
