Stem Cell Therapy for Burns: Story so Far

Figures & data

Figure 1 Current treatment approaches for burn wound coverage.

Notes: (A) Autologous split-thickness skin graft. (B) AlloSkin^TM skin allograft. (C) Cultured epithelial autograft. Reproduced from: Chua AWC, Khoo YC, Tan BK, Tan KC, Foo CL, Chong SJ. Skin tissue engineering advances in severe burns: review and therapeutic applications. Burns & Trauma. 2016;4:s41038–016–0027–y.¹²¹ Copyright © 2016, Oxford University Press. Creative Commons CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/legalcode). (D) Integra® Dermal Regenerative Template. (E) Self-assembled bilayer skin substitute of dermal and epidermal structures. Data from Rangatchew et al.¹¹⁹ (F) Recell/cell spray which sprays a suspension of skin cells directly to wounded area. Created with Biorender.

Table 1 Various Sources of Stem Cells and Their Characteristics in Burn Wound Healing

Source	Wound Healing Mechanism	Advantages
Hair follicle stem cells (HFSC)	● Generate stratified epidermis, hair follicle cells and keratinocytes	Easily accessible
Embryonic stem cells (ESC)	● Enhance re-epithelialization, cell proliferation and vascularization	Generate all three germ layers. Disadvantage: Ethically controversial
Umbilical cord stem cells (USC)	● Have endothelial progenitor cells, hematopoietic and non-hematopoietic cells ● Differentiate into epithelium in vivo and in vitro ● Reduce inflammation ● Immunomodulatory	Non-controversial
Bone marrow-derived stem cells (BM-MSC)	● Increases collagen production and reduces scar formation ● Decrease MMP production	High rate of proliferation and differentiation. Disadvantage: Low yield
Adipose tissue -derived stem cells (AD-MSC)	● Promote angiogenesis ● Immunomodulatory ● Reduces scar formation	High yield and easily obtainable, can be isolated from discarded burned skin
Burn-derived mesenchymal stem cells (BD-MSC)	● No tumorigenicity ● Promote re-epithelialization ● Reduce granulation ● Function unaffected by thermal damage	Safe source

Figure 2 Different pathways used by stem cells in wound healing.

Notes: (A) PI3K/AKT pathway. (B) Notch Pathway. (C) Wnt/B-catenin pathway. (D) TGF-β pathway. (E) Hedgehog pathway.

Figure 3 Exosome isolation from stem cells.

Notes: 1. Schematic representing the presence of membrane-bound extracellular vesicles in media of stem cell cultures. 2. Removal of cell debris from supernatant media to subsequently purify for exosomes. 3. Exosome isolation and purification. Exosomes are a versatile therapeutic option for burn wound healing that can be either directly injected or embedded in scaffolds. Exosomes stimulate wound healing via PI3K/AKT, Wnt/b-catenin, SHH, notch and TGF-b pathways. Created with Biorender.

Figure 4 Secretome of stem cells.

Notes: Supernatant media of stem cell cultures contains growth factors, cytokines, chemokines and extracellular vesicles that can be purified using ultra-centrifugation filtration units and provide the opportunity to select for certain secretome molecules based on their molecular weights. Secretome of stem cells provides a cell-free universal therapeutic option for wound healing that can potentially have the same benefit as cells but negates the challenges with viability and immune rejection.

Figure 5 Different modes of delivery of stem cells/secretome for burn wounds. Stem cells and their products can be delivered onto burn wounds either as direct local injection, delivered in a supportive matrix such as fibrin or embedded with in scaffold matrices. Such approaches improve sustained delivery of therapeutics factors and/or maintain cell viability.

Figure 6 Proportion of stem cell clinical trials in areas of skin regeneration among other indications.

Note: Data adapted from Kabat et al.¹²⁰

Chua AWC, Khoo YC, Tan BK, Tan KC, Foo CL, Chong SJ. Skin tissue engineering advances in severe burns: review and therapeutic applications Burns & Trauma. 2016;4:s41038–016–0027–y. doi:10.1186/s41038-016-0027-y

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Rangatchew F, Vester-Glowinski P, Rasmussen BS, et al. Mesenchymal stem cell therapy of acute thermal burns: a systematic review of the effect on inflammation and wound healing. Burns. 2021;47(2):270–294. doi:10.1016/j.burns.2020.04.012

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Kabat M, Bobkov I, Kumar S, Grumet M. Trends in mesenchymal stem cell clinical trials 2004–2018: is efficacy optimal in a narrow dose range? Stem Cells Transl Med. 2020;9(1):17–27. doi:10.1002/sctm.19-0202

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