Regenerative Medicine in Dermatology

authors:

avatar Mohammad Ali Nilforoushzadeh 1 , 2 , avatar Mohammad Amir Amirkhani 1 , 3 , avatar Farnoosh Seirafianpour ORCID 4 , avatar Yeganeh Pakbaz ORCID 4 , avatar Sona Zare ORCID 1 , 5 , ** , avatar Azadeh Goodarzi ORCID 6 , 1 , *

Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Tehran, Iran
Stem Cell and Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Corresponding Authors:

how to cite: Nilforoushzadeh M A, Amirkhani M A, Seirafianpour F, Pakbaz Y, Zare S, et al. Regenerative Medicine in Dermatology. J Skin Stem Cell. 2022;9(1):e124222. https://doi.org/10.5812/jssc-124222.

Dear Editor,

Regenerative medicine is a developing field of medicine that has been used in both labs and clinics with the main aim of healing damaged parts through repairing, replacing, and regenerating the cell of the body (1, 2). Regenerative medicine, including soluble molecules (proteins, cytokines, growth factors), biomaterials (biomaterials are natural or synthetic substances used for the creation of skin substitutes in clinical applications), tissue engineering (in dermatology, numerous studies in the field of tissue engineering have been translated already into therapeutical applications, like for the treatment of chronic wounds), gene therapy (gene therapy approach is perfectly eligible for the treatment of diseases involving recessive loss-of-function mutations, as it occurs in junctional or recessive dystrophic epidermolysis bullosa (EB)), cell therapy (bone marrow and adipose mesenchymal stem cells present further suitable candidates for cell therapy) and cell reprogramming (induced pluripotent stem cells (iPS) were phenotypically and functionally indistinguishable from embryonic stem cells). Because of its easy accessibility, skin is becoming an attractive organ, and as the largest organ of the body, it is one of the most marked fields to step through (2). While there are many common acquired and inherited cutaneous pathologies, such as burns, diabetic ulcers, psoriasis, and vitiligo, which mostly are not well-treated and there is no gold standard treatment for them, regenerative medicine impresses as a novel and promising choice of treatment, both as monotherapy and combination therapy with other operative therapeutics in dermatology (3, 4). Over the last two decades, fundamental advances have been made using scaffolds and cell types in this fast-growing area (5).

Mesenchymal stem cells (MSCs) are adult stem cells, which can be isolated from human sources (such as the dermis, adipose, and hypodermis. MSCs are mesodermal in origin and have the capacity to differentiate into different cells (6). MSCs have been greatly studied and can migrate towards injured areas in response to inflammation, differentiating into cells, like fibroblasts, adipose tissue, bone, and other mesenchymal lineages and then secreting pro-regenerative cytokines, chemokines, and growth factors (6). Therefore, MSCs have become the most promising therapeutic options for wound healing, increasing angiogenesis, and cancer (6). Adipose stem cells (ASCs) are among the best choices in wound healing procedures and many other purposes, like skin rejuvenile and skin remodeling, because of their capability of differentiating in various cells, promoting angiogenesis, and secreting numerous cytokines (7). Compared to the other stem cells harvested from the bone marrow, ASCs are higher in yields and more simply accessible (7).

Extracellular vesicles (EV), formerly called exosomes, are nano-sized vesicles containing specific nucleic acids, proteins, and lipids capable of cell-to-cell mediator transferring that has made them unique; hence, they can be utilized as a therapeutic and diagnostic tool in this field (8, 9). MSC-exosomes have shown anti-inflammatory, anti-aging, and wound healing properties and have been highly considered (8, 9).

Platelet-rich plasma (PRP) is plasma with a significant additional level of concentrated platelets that are obtained through centrifuging whole blood (10). Platelets are characterized by alpha granules containing a great load of growth factors and cytokines affecting homeostasis, tissue repairing, and collagen production (10, 11).

Stem cells-conditioned media (SCs-CM) or secretome contains several growth factors and cytokines; thus, it may be used as a better alternative to cell therapy, which needs to be elucidated. SCs-CM is where stem cells are cultured and secreted proteins, lipids, nucleic acids, and EVs (12). The interest in this method would be the potency of being produced in extensive quantities and preserved for a greater time without losing its efficacy (12, 13).

Regenerative medicine has been applied clinically in conditions, such as inflammatory and autoimmune diseases (e.g., systematic lupus erythematosus (14), and vitiligo (15)), scar healing (e.g., diabetic foot ulcer (16)), and cosmetic fields (e.g., skin resurfacing (17)).

Studies have revealed that PRP is an effective technique in treating vitiligo, and also it has a synergic effect with fractional CO2 (15, 18). MSCs have been beneficial due to differentiating into keratinocytes, secreting numerous growth factors, and increasing the speed of wound closure (16).

Wang et al. have shown that MSCs, especially umbilical cord-derived stem cells, are associated with advantages in treating SLE (19). Studies have demonstrated that PRP, as an adjuvant to laser therapy and EVs, is so effective, especially on facial skin (20-24).

As mentioned above, regenerative medicine has shown promising results in dermatology. Given the rapidly developing nature of regenerative medicine, it will soon expand to other dermatology fields and transform treatment methods, leading to improvement in patients' health and quality of life.

Acknowledgements

References

  • 1.

    Greenwood HL, Singer PA, Downey GP, Martin DK, Thorsteinsdottir H, Daar AS. Regenerative medicine and the developing world. PLoS Med. 2006;3(9). e381. [PubMed ID: 16968130]. [PubMed Central ID: PMC1564180]. https://doi.org/10.1371/journal.pmed.0030381.

  • 2.

    Dieckmann C, Renner R, Milkova L, Simon JC. Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyond. Exp Dermatol. 2010;19(8):697-706. [PubMed ID: 20545761]. https://doi.org/10.1111/j.1600-0625.2010.01087.x.

  • 3.

    Petrof G, Abdul-Wahab A, McGrath JA. Cell therapy in dermatology. Cold Spring Harb Perspect Med. 2014;4(6). [PubMed ID: 24890834]. [PubMed Central ID: PMC4031958]. https://doi.org/10.1101/cshperspect.a015156.

  • 4.

    Sierra-Sanchez A, Montero-Vilchez T, Quinones-Vico MI, Sanchez-Diaz M, Arias-Santiago S. Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases. Front Cell Dev Biol. 2021;9:643125. [PubMed ID: 33768095]. [PubMed Central ID: PMC7985058]. https://doi.org/10.3389/fcell.2021.643125.

  • 5.

    Nilforoushzadeh MA, Amirkhani MA, Hamidieh AA, Seifalian AM, Sisakht MM. Skin regenerative medicine advancements in the Islamic Republic of Iran: a concise review. Regen Med. 2019;14(11):1047-56. [PubMed ID: 31718464]. https://doi.org/10.2217/rme-2018-0170.

  • 6.

    Lee DE, Ayoub N, Agrawal DK. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther. 2016;7:37. [PubMed ID: 26960535]. [PubMed Central ID: PMC4784457]. https://doi.org/10.1186/s13287-016-0303-6.

  • 7.

    Koo MA, Hee Hong S, Hee Lee M, Kwon BJ, Mi Seon G, Sung Kim M, et al. Effective stacking and transplantation of stem cell sheets using exogenous ROS-producing film for accelerated wound healing. Acta Biomater. 2019;95:418-26. [PubMed ID: 30660002]. https://doi.org/10.1016/j.actbio.2019.01.019.

  • 8.

    Casado-Diaz A, Quesada-Gomez JM, Dorado G. Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing. Front Bioeng Biotechnol. 2020;8:146. [PubMed ID: 32195233]. [PubMed Central ID: PMC7062641]. https://doi.org/10.3389/fbioe.2020.00146.

  • 9.

    Ha DH, Kim HK, Lee J, Kwon HH, Park GH, Yang SH, et al. Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells. 2020;9(5). [PubMed ID: 32392899]. [PubMed Central ID: PMC7290908]. https://doi.org/10.3390/cells9051157.

  • 10.

    Sirithanabadeekul P, Dannarongchai A, Suwanchinda A. Platelet-rich plasma treatment for melasma: A pilot study. J Cosmet Dermatol. 2020;19(6):1321-7. [PubMed ID: 31568636]. https://doi.org/10.1111/jocd.13157.

  • 11.

    Merchan WH, Gomez LA, Chasoy ME, Alfonso-Rodriguez CA, Munoz AL. Platelet-rich plasma, a powerful tool in dermatology. J Tissue Eng Regen Med. 2019;13(5):892-901. [PubMed ID: 30793521]. https://doi.org/10.1002/term.2832.

  • 12.

    Rhatomy S, Prasetyo TE, Setyawan R, Soekarno NR, Romaniyanto F, Sedjati AP, et al. Prospect of stem cells conditioned medium (secretome) in ligament and tendon healing: A systematic review. Stem Cells Transl Med. 2020;9(8):895-902. [PubMed ID: 32304180]. [PubMed Central ID: PMC7381802]. https://doi.org/10.1002/sctm.19-0388.

  • 13.

    Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int. 2014;2014:965849. [PubMed ID: 25530971]. [PubMed Central ID: PMC4229962]. https://doi.org/10.1155/2014/965849.

  • 14.

    Marfia G, Navone SE, Di Vito C, Ughi N, Tabano S, Miozzo M, et al. Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds. Organogenesis. 2015;11(4):183-206. [PubMed ID: 26652928]. [PubMed Central ID: PMC4879897]. https://doi.org/10.1080/15476278.2015.1126018.

  • 15.

    Mercuri SR, Vollono L, Paolino G. The Usefulness of Platelet-Rich Plasma (PRP) for the Treatment of Vitiligo: State of the Art and Review. Drug Des Devel Ther. 2020;14:1749-55. [PubMed ID: 32440100]. [PubMed Central ID: PMC7213865]. https://doi.org/10.2147/DDDT.S239912.

  • 16.

    Andrews KL, Houdek MT, Kiemele LJ. Wound management of chronic diabetic foot ulcers: from the basics to regenerative medicine. Prosthet Orthot Int. 2015;39(1):29-39. [PubMed ID: 25614499]. https://doi.org/10.1177/0309364614534296.

  • 17.

    Boddu S, Hashim PW, Nia JK, Horowitz R, Farberg A, Goldenberg G. Regenerative medicine in cosmetic dermatology. Cutis. 2018;101(1):33-6. [PubMed ID: 29529112].

  • 18.

    Zhang M, Park G, Zhou B, Luo D. Applications and efficacy of platelet-rich plasma in dermatology: A clinical review. J Cosmet Dermatol. 2018;17(5):660-5. [PubMed ID: 30047234]. https://doi.org/10.1111/jocd.12673.

  • 19.

    Wang S, Zhu R, Li H, Li J, Han Q, Zhao RC. Mesenchymal stem cells and immune disorders: from basic science to clinical transition. Front Med. 2019;13(2):138-51. [PubMed ID: 30062557]. https://doi.org/10.1007/s11684-018-0627-y.

  • 20.

    Badran KW, Nabili V. Lasers, Microneedling, and Platelet-Rich Plasma for Skin Rejuvenation and Repair. Facial Plast Surg Clin North Am. 2018;26(4):455-68. [PubMed ID: 30213427]. https://doi.org/10.1016/j.fsc.2018.06.007.

  • 21.

    Tonnard P, Verpaele A, Carvas M. Fat Grafting for Facial Rejuvenation with Nanofat Grafts. Clin Plast Surg. 2020;47(1):53-62. [PubMed ID: 31739897]. https://doi.org/10.1016/j.cps.2019.08.006.

  • 22.

    Nilforoushzadeh MA, Heidari-Kharaji M, Alavi S, Nouri M, Nikkhah N, Jahangiri F, et al. Transplantation of autologous fat, stromal vascular fraction (SVF) cell, and platelet-rich plasma (PRP) for cell therapy of atrophic acne scars: Clinical evaluation and biometric assessment. J Cosmet Dermatol. 2021. [PubMed ID: 34228901]. https://doi.org/10.1111/jocd.14333.

  • 23.

    Nilforoushzadeh M, Rahimi Jameh E, Jaffary F, Abolhasani E, Keshtmand G, Zarkob H, et al. Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice. Cell J. 2017;19(2):259-68. [PubMed ID: 28670518]. [PubMed Central ID: PMC5412784]. https://doi.org/10.22074/cellj.2016.3916.

  • 24.

    Nilforoushzadeh MA, Aghdami N, Taghiabadi E. Human Hair Outer Root Sheath Cells and Platelet-Lysis Exosomes Promote Hair Inductivity of Dermal Papilla Cell. Tissue Eng Regen Med. 2020;17(4):525-36. [PubMed ID: 32519329]. [PubMed Central ID: PMC7392975]. https://doi.org/10.1007/s13770-020-00266-4.