Giedre RAMANAUSKAITE, Aida VAITKUVIENE, Vytautas KASETA, Ausra VITLIPAITE, Ausra LIUBAVICIUTE, Gene BIZIULEVICIENE

Bone marrow-derived lineage-negative cells accelerate skin regeneration in vivo

Cell-based therapy is a promising strategy for promoting tissue regeneration when conventional treatments are not effective.The choice of the accessible source to obtain a sufficient cell amount and the use of suitable biomaterials to improve the cell deliveryefficiency are the main tasks for safe, effective, and reliable application of stem cell therapy. In this study, we have compared the influenceof bone marrow-derived Lin¯ cells on skin regeneration after local transplantation with or without type I collagen-based gel in a BALB/cmice full-thickness wound model. Lin¯ cells were isolated using magnetic-associated cell sorting and identified by flow cytometry.Cytokine gene expression was examined using real-time PCR. Our results show that the bone marrow-derived Lin¯ cell populationdemonstrates the properties to stimulate the skin tissue regeneration. Significant accelerated wound closure was revealed after celltransplantation (P < 0.05). Histological analysis indicated the earliest inhibition of inflammation, accelerated reepithelialization, andevenly distributed skin appendages in the neodermis after Lin¯ cell transplantation with type I collagen gel. The significant changes inmRNA levels of cytokines TNF-α, IL-10, TGF-β, and VEGF after Lin¯ cell transplantation were confirmed by RT-PCR (P < 0.05). Theability to positively control the reactions taking place during the wound healing process gives the advantage to the bone marrow Lin¯cell population to be used as a cell source for therapy.

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Anthony DF, Shiels PG (2013). Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs. Transplant Res 2: 10-18.
Arno A, Smith AH, Blit PH, Shehab MA, Gauglitz GG, Jeschke MG (2011). Stem cell therapy: a new treatment for burns? Pharmaceuticals 4: 1355-1380.
Arun KR, Sathish KD, Nishanth T (2011). A review on stem cell research & their role in various diseases. J Stem Cell Res Ther 1: 112-117.
Badiavas EV, Abedi M, Butmarc J, Falanga V, Quesenberry P (2003). Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol 196: 245-250.
Baraniak PR, McDevitt TC (2010). Stem cell paracrine actions and tissue regeneration. Regen Med 5: 121-143.
Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008). Growth factors and cytokines in wound healing. Wound Repair Regen 16: 585-601.
Bertozzi N, Simonacci F, Grieco MP, Grignaffini E, Raposio E (2017). The biological and clinical basis for the use of adipose-derived stem cells in the field of wound healing. Ann Med Surg (Lond) 20: 41-48.
Burd A, Ahmed K, Lam S, Ayyappan T, Huang L (2007). Stem cell strategies in burns care. Burns 33: 282-291.
Grote K, Petri M, Liu C, Jehn P, Spalthoff S, Kokemüller H, Luchtefeld M, Tschernig T, Krettek C, Haasper C et al. (2013). Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors. Eur Cell Mater 26: 66-79.
Huang SP, Hsu CC, Chang SC, Wang CH, Deng SC, Dai NT, Chen TM, Chan JY, Chen SG, Huang SM (2012). Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect. Ann Plast Surg 69: 656-662.
Kim JY, Suh W (2010). Stem cell therapy for dermal wound healing. Int J Stem Cells 3: 29-31.
Lee DE, Ayoub N, Agrawal DK (2016). Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther 7: 37-45.
Li Y, Zheng L, Xu X, Song L, Li Y, Li W, Zhang S, Zhang F, Jin H (2013). Mesenchymal stem cells modified with angiopoietin-1 gene promote wound healing. Stem Cell Res Ther 4: 113-123.
Lin CD, Allori AC, Macklin JE, Sailon AM, Tanaka R, Levine JP, Saadeh PB, Warren SM (2008). Topical lineage-negative progenitor-cell therapy for diabetic wounds. Plast Reconstr Surg 122: 1341-1351.
Liu H, Lu K, MacAry PA, Wong KL, Heng A, Cao T, Kemeny DM (2012). Soluble molecules are key in maintaining the immunomodulatory activity of murine mesenchymal stromal cells. J Cell Sci 125: 200-208.
Murawala P, Tanaka EM, Currie JD (2012). Regeneration: The ultimate example of wound healing. Semin Cell Dev Biol 23: 954-962.
Pedroso DCS, Tellechea A, Moura L, Fidalgo-Carvalho I, Duarte J, Carvalho E, Ferreira L (2011). Improved survival, vascular differentiation and wound healing potential of stem cells cocultured with endothelial cells. PLoS One 6: e16114.
Qing C (2017). The molecular biology in wound healing & non-healing wound. Chin J Traumatol 20:189-193.
Ramanauskaite G, Kaseta V, Vaitkuviene A, Biziuleviciene G (2010). Skin regeneration with bone marrow-derived cell populations. Int Immunopharmacol 10: 1548-1551.
Ramanauskaite G, Zalalyte D, Kaseta V, Vaitkuviene A, Kalediene L, Biziuleviciene G (2014). Skin extracellular matrix components accelerate the regenerative potential of Lin– cells. Cent Eur J Biol 9: 367-373.
Ratajczak MZ, Kucia M, Majka M, Reca R, Ratajczak J (2004). Heterogeneous populations of bone marrow stem cells--are we spotting on the same cells from the different angles? Folia Histochem Cytobiol 42: 139-146.
Rustad KC, Wong VW, Sorkin M, Glotzbach JP, Major MR, Rajadas J, Longaker MT, Gurtner GC (2012). Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials 33: 80-90.
Srijaya TC, Ramasamy TS, Kasim NH (2014). Advancing stem cell therapy from bench to bedside: lessons from drug therapies. J Transl Med 12: 243-252.
Wu Y, Wang J, Scott PG, Tredget EE (2007). Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen 1: S18-26.
Yu SP, Wei Z, Wei L (2013). Preconditioning strategy in stem cell transplantation therapy. Transl Stroke Res 4: 76-88.
Zhang C, Fu X (2008). Therapeutic potential of stem cells in skin repair and regeneration. Chin J Traumatol 11: 209-221.