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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Review Article

Delayed Wound Healing in the Elderly and a New Therapeutic Target: CD271

Author(s): Hongqing Zhao, Sirui Fan and Jiachen Sun*

Volume 19, Issue 3, 2024

Published on: 19 April, 2023

Page: [316 - 323] Pages: 8

DOI: 10.2174/1574888X18666230403083603

Price: $65

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Abstract

With the development of society, the global population is showing a trend of aging. It is well known that age is one of the factors affecting wound healing. Aging compromises the normal physiological process of wound healing, such as the change of skin structure, the decrease of growth factors, the deceleration of cell proliferation, and the weakening of migration ability, hence delaying wound healing. At present, research in adult stem cell-related technology and its derived regenerative medicine provides a novel idea for the treatment of senile wounds. Studies have confirmed that CD271 (P75 neurotropism receptor/P75NTR)-positive cells (CD271+ cells) are a kind of stem cells with a stronger ability of proliferation, differentiation, migration and secretion than CD271 negative (CD271- cells). Meanwhile, the total amount and distribution of CD271 positive cells in different ages of skin are also different, which may be related to the delayed wound healing of aging skin. Therefore, this article reviews the relationship between CD271+ cells and senile wounds and discusses a new scheme for the treatment of senile wounds.

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[1]
Morita S, Mochizuki M, Wada K, et al. Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells. Cancer Lett 2019; 461: 144-52.
[http://dx.doi.org/10.1016/j.canlet.2019.07.011] [PMID: 31325530]
[2]
Murillo-Sauca O, Chung MK, Shin JH, et al. CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget 2014; 5(16): 6854-66.
[http://dx.doi.org/10.18632/oncotarget.2269] [PMID: 25149537]
[3]
Sharpless NE, DePinho RA. How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 2007; 8(9): 703-13.
[http://dx.doi.org/10.1038/nrm2241] [PMID: 17717515]
[4]
Foerster Y, Stöver T, Wagenblast J, et al. Relevance of neurotrophin receptors CD271 and TrkC for prognosis, migration, and proliferation in head and neck squamous cell carcinoma. Cells 2019; 8(10): 1167.
[5]
Hasebe Y, Hasegawa S, Hashimoto N, et al. Analysis of cell characterization using cell surface markers in the dermis. J Dermatol Sci 2011; 62(2): 98-106.
[http://dx.doi.org/10.1016/j.jdermsci.2011.01.012] [PMID: 21382697]
[6]
Truzzi F, Saltari A, Palazzo E, et al. CD271 mediates stem cells to early progeny transition in human epidermis. J Invest Dermatol 2015; 135(3): 786-95.
[http://dx.doi.org/10.1038/jid.2014.454] [PMID: 25330297]
[7]
Akamatsu H, Hasegawa S, Yamada T, et al. Age-related decrease in CD271 + cells in human skin. J Dermatol 2016; 43(3): 311-3.
[http://dx.doi.org/10.1111/1346-8138.13048] [PMID: 26300383]
[8]
Bosset S, Barré P, Chalon A, et al. Skin ageing: Clinical and histopathologic study of permanent and reducible wrinkles. Eur J Dermatol 2002; 12(3): 247-52.
[PMID: 11978565]
[9]
Yamamoto N, Akamatsu H, Hasegawa S, et al. Isolation of multipotent stem cells from mouse adipose tissue. J Dermatol Sci 2007; 48(1): 43-52.
[http://dx.doi.org/10.1016/j.jdermsci.2007.05.015] [PMID: 17644316]
[10]
Khavkin J, Ellis DAF. Aging skin: Histology, physiology, and pathology. Facial Plast Surg Clin North Am 2011; 19(2): 229-34.
[http://dx.doi.org/10.1016/j.fsc.2011.04.003] [PMID: 21763983]
[11]
Bonté F, Girard D, Archambault JC, Desmoulière A. Skin changes during ageing. Subcell Biochem 2019; 91: 249-80.
[http://dx.doi.org/10.1007/978-981-13-3681-2_10] [PMID: 30888656]
[12]
Bernstein EF, Chen YQ, Kopp JB, et al. Long-term sun exposure alters the collagen of the papillary dermis. Comparison of sun-protected and photoaged skin by northern analysis, immunohistochemical staining, and confocal laser scanning microscopy. J Am Acad Dermatol 1996; 34(2 Pt 1): 209-18.
[http://dx.doi.org/10.1016/S0190-9622(96)80114-9] [PMID: 8642084]
[13]
Lovell CR, Smolenski KA, Duance VC, Light ND, Young S, Dyson M. Type I and III collagen content and fibre distribution in normal human skin during ageing. Br J Dermatol 1987; 117(4): 419-28.
[http://dx.doi.org/10.1111/j.1365-2133.1987.tb04921.x] [PMID: 3676091]
[14]
Montagna W, Carlisle K. Structural changes in aging human skin. J Invest Dermatol 1979; 73(1): 47-53.
[http://dx.doi.org/10.1111/1523-1747.ep12532761] [PMID: 448177]
[15]
Kurban RS, Bhawan J. Histologic changes in skin associated with aging. J Dermatol Surg Oncol 1990; 16(10): 908-14.
[http://dx.doi.org/10.1111/j.1524-4725.1990.tb01554.x] [PMID: 2229632]
[16]
Jahroomishirazi R, Bader A, Ebert S, et al. Isolation and characterization of CD271<sup>+</sup> stem cells derived from sheep dermal skin. Cells Tissues Organs 2014; 200(2): 141-52.
[http://dx.doi.org/10.1159/000381534] [PMID: 25997892]
[17]
Victorelli S. Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction. EMBO J 2019; 38(23): e101982.
[18]
Zhang M, Cao Y, Li X, et al. Cd271 mediates proliferation and differentiation of epidermal stem cells to support cutaneous burn wound healing. Cell Tissue Res 2018; 371(2): 273-82.
[http://dx.doi.org/10.1007/s00441-017-2723-8] [PMID: 29150821]
[19]
Tsuchida Y. The effect of aging and arteriosclerosis on human skin blood flow. J Dermatol Sci 1993; 5(3): 175-81.
[http://dx.doi.org/10.1016/0923-1811(93)90764-G] [PMID: 8241073]
[20]
Gniadecka M, Serup J, Søndergaard J. Age-related diurnal changes of dermal oedema: Evaluation by high-frequency ultrasound. Br J Dermatol 1994; 131(6): 849-55.
[http://dx.doi.org/10.1111/j.1365-2133.1994.tb08588.x] [PMID: 7857838]
[21]
Farage MA, Miller KW, Elsner P, Maibach HI. Intrinsic and extrinsic factors in skin ageing: A review. Int J Cosmet Sci 2008; 30(2): 87-95.
[http://dx.doi.org/10.1111/j.1468-2494.2007.00415.x] [PMID: 18377617]
[22]
Pochi PE, Strauss JS, Downing DT. Age-related changes in sebaceous gland activity. J Invest Dermatol 1979; 73(1): 108-11.
[http://dx.doi.org/10.1111/1523-1747.ep12532792] [PMID: 448169]
[23]
Bonham CA, Kuehlmann B, Gurtner GC. Impaired neovascularization in aging. Adv Wound Care 2020; 9(3): 111-26.
[http://dx.doi.org/10.1089/wound.2018.0912]
[24]
Nguyen HP, Katta R. Sugar Sag: Glycation and the role of diet in aging skin. Skin Therapy Lett 2015; 20(6): 1-5.
[PMID: 27224842]
[25]
Tashkin DP, Murray HE, Skeans M, Murray RP. Skin manifestations of inhaled corticosteroids in COPD patients: Results from Lung Health Study II. Chest 2004; 126(4): 1123-33.
[http://dx.doi.org/10.1016/S0012-3692(15)31287-3] [PMID: 15486373]
[26]
Bentov I, Reed MJ. Anesthesia, microcirculation, and wound repair in aging. Anesthesiology 2014; 120(3): 760-72.
[http://dx.doi.org/10.1097/ALN.0000000000000036] [PMID: 24195972]
[27]
Pal R, Singh SN, Chatterjee A, Saha M. Age-related changes in cardiovascular system, autonomic functions, and levels of BDNF of healthy active males: role of yogic practice. Age 2014; 36(4): 9683.
[http://dx.doi.org/10.1007/s11357-014-9683-7] [PMID: 25012275]
[28]
Brubaker AL, Rendon JL, Ramirez L, Choudhry MA, Kovacs EJ. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age. J Immunol 2013; 1904: 1746-57.
[http://dx.doi.org/10.4049/jimmunol.1201213]
[29]
Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: A mini-review. Gerontology 2013; 59(2): 159-64.
[http://dx.doi.org/10.1159/000342344] [PMID: 23108154]
[30]
Wilkinson HN, Hardman MJ. Senescence in wound repair: Emerging strategies to target chronic healing wounds. Front Cell Dev Biol 2020; 8: 773.
[http://dx.doi.org/10.3389/fcell.2020.00773] [PMID: 32850866]
[31]
Altavilla D, Saitta A, Cucinotta D, et al. Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse. Diabetes 2001; 50(3): 667-74.
[http://dx.doi.org/10.2337/diabetes.50.3.667] [PMID: 11246889]
[32]
Greaves NS, Ashcroft KJ, Baguneid M, Bayat A. Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci 2013; 72(3): 206-17.
[http://dx.doi.org/10.1016/j.jdermsci.2013.07.008] [PMID: 23958517]
[33]
Peake MA, Caley M, Giles PJ, et al. Identification of a transcriptional signature for the wound healing continuum. Wound Repair Regen 2014; 22(3): 399-405.
[http://dx.doi.org/10.1111/wrr.12170] [PMID: 24844339]
[34]
Nall AV, Brownlee RE, Colvin CP, et al. Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats. Arch Otolaryngol Head Neck Surg 1996; 122(2): 171-7.
[http://dx.doi.org/10.1001/archotol.1996.01890140057011] [PMID: 8630211]
[35]
Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF-β family in wound healing, burns and scarring: A review. Int J Burns Trauma 2012; 2(1): 18-28.
[PMID: 22928164]
[36]
Zorin V, Zorina A, Smetanina N, et al. Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation. Aging 2017; 9(5): 1404-13.
[http://dx.doi.org/10.18632/aging.101240]
[37]
Sadoun E, Reed MJ. Impaired angiogenesis in aging is associated with alterations in vessel density, matrix composition, inflammatory response, and growth factor expression. J Histochem Cytochem 2003; 51(9): 1119-30.
[http://dx.doi.org/10.1177/002215540305100902] [PMID: 12923237]
[38]
Kim DJ, Mustoe T, Clark RAF. Cutaneous wound healing in aging small mammals: A systematic review. Wound Repair Regen 2015; 23(3): 318-39.
[http://dx.doi.org/10.1111/wrr.12290] [PMID: 25817246]
[39]
Beckert S, Haack S, Hierlemann H, et al. Stimulation of steroid-suppressed cutaneous healing by repeated topical application of IGF-I: Different mechanisms of action based upon the mode of IGF-I delivery. J Surg Res 2007; 139(2): 217-21.
[http://dx.doi.org/10.1016/j.jss.2006.08.006] [PMID: 17070552]
[40]
Liarte S, Bernabé-García Á, Nicolás FJ. Role of TGF-β in skin chronic wounds: A keratinocyte perspective. Cells 2020; 9(2): 306.
[http://dx.doi.org/10.3390/cells9020306] [PMID: 32012802]
[41]
Reed MJ, Corsa AC, Kudravi SA, McCormick RS, Arthur WT. A deficit in collagenase activity contributes to impaired migration of aged microvascular endothelial cells. J Cell Biochem 2000; 77(1): 116-26.
[http://dx.doi.org/10.1002/(SICI)1097-4644(20000401)77:1<116:AID-JCB12>3.0.CO;2-7] [PMID: 10679822]
[42]
Bond JS, Duncan JAL, Sattar A, et al. Maturation of the human scar: An observational study. Plast Reconstr Surg 2008; 121(5): 1650-8.
[http://dx.doi.org/10.1097/PRS.0b013e31816a9f6f] [PMID: 18453989]
[43]
Oh S. Combined treatment of monopolar and bipolar radiofrequency increases skin elasticity by decreasing the accumulation of advanced glycated end products in aged animal skin. Int J Mol Sci 2022; 23(6)
[44]
Anastasia A, Barker PA, Chao MV, Hempstead BL. Detection of p75NTR trimers: Implications for receptor stoichiometry and activation. J Neurosci 2015; 35(34): 11911-20.
[http://dx.doi.org/10.1523/JNEUROSCI.0591-15.2015] [PMID: 26311773]
[45]
Zhang N, Yuan W, Fan JS, Lin Z. Structure of the C-terminal domain of TRADD reveals a novel fold in the death domain superfamily. Sci Rep 2017; 7(1): 7073.
[http://dx.doi.org/10.1038/s41598-017-07348-9] [PMID: 28765645]
[46]
Maffioli E. Brain proteome and behavioural analysis in wild type, BDNF +/- and BDNF -/- Adult Zebrafish (Danio rerio) exposed to two different temperatures. Int J Mol Sci 2022; 23(10)
[47]
Lehraiki A, Cerezo M, Rouaud F, et al. Increased CD271 expression by the NF-kB pathway promotes melanoma cell survival and drives acquired resistance to BRAF inhibitor vemurafenib. Cell Discov 2015; 27(1): 15030.
[http://dx.doi.org/10.1038/celldisc.2015.30]
[48]
Shu YH, Lu XM, Wei JX, Xiao L, Wang YT. Update on the role of p75NTR in neurological disorders: A novel therapeutic target. Biomed Pharmacother 2015; 76: 17-23.
[http://dx.doi.org/10.1016/j.biopha.2015.10.010] [PMID: 26653545]
[49]
Bothwell M. Recent advances in understanding neurotrophin signaling. F1000Res 2016; 5: F1000. Faculty Rev- 1885.
[50]
Nielsen PS, Riber-Hansen R, Steiniche T. Immunohistochemical CD271 expression correlates with melanoma progress in a case-control study. Pathology 2018; 50(4): 402-10.
[http://dx.doi.org/10.1016/j.pathol.2017.12.340] [PMID: 29678478]
[51]
Mochizuki M, Tamai K, Imai T, et al. CD271 regulates the proliferation and motility of hypopharyngeal cancer cells. Sci Rep 2016; 29(6): 30707.
[http://dx.doi.org/10.1038/srep30707]
[52]
Nakamura T, Endo K, Kinoshita S. Identification of human oral keratinocyte stem/progenitor cells by neurotrophin receptor p75 and the role of neurotrophin/p75 signaling. Stem Cells 2007; 25(3): 628-38.
[http://dx.doi.org/10.1634/stemcells.2006-0494] [PMID: 17110619]
[53]
Okumura T, Shimada Y, Imamura M, Yasumoto S. Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro. Oncogene 2003; 22(26): 4017-26.
[http://dx.doi.org/10.1038/sj.onc.1206525] [PMID: 12821936]
[54]
Latifi-Pupovci H, Kuçi Z, Wehner S, et al. In vitro migration and proliferation (“wound healing”) potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells. J Transl Med 2015; 25(13): 315.
[55]
Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37(5): 1528-42.
[http://dx.doi.org/10.1177/147323000903700531] [PMID: 19930861]
[56]
Iwata Y, Akamatsu H, Hasebe Y, Hasegawa S, Sugiura K. Skin-resident stem cells and wound healing. Nihon Rinsho Meneki Gakkai Kaishi 2017; 40(1): 1-11.
[http://dx.doi.org/10.2177/jsci.40.1] [PMID: 28539548]
[57]
Nieto-Estévez V, Pignatelli J, Araúzo-Bravo MJ, Hurtado-Chong A, Vicario-Abejón C. A global transcriptome analysis reveals molecular hallmarks of neural stem cell death, survival, and differentiation in response to partial FGF-2 and EGF deprivation. PLoS One 2013; 8(1): e53594.
[http://dx.doi.org/10.1371/journal.pone.0053594] [PMID: 23308259]
[58]
Zouboulis CC, Adjaye J, Akamatsu H, Moe-Behrens G, Niemann C. Human skin stem cells and the ageing process. Exp Gerontol 2008; 43(11): 986-97.
[http://dx.doi.org/10.1016/j.exger.2008.09.001] [PMID: 18809487]
[59]
Iwata Y, Hasebe Y, Hasegawa S, et al. Dermal CD271+ cells are closely associated with regeneration of the dermis in the wound healing process. Acta Derm Venereol 2017; 97(5): 593-600.
[http://dx.doi.org/10.2340/00015555-2624] [PMID: 28127619]
[60]
Zhang M, Zhang R, Li X, et al. CD271 promotes STZ-induced diabetic wound healing and regulates epidermal stem cell survival in the presence of the pTrkA receptor. Cell Tissue Res 2020; 379(1): 181-93.
[http://dx.doi.org/10.1007/s00441-019-03125-4] [PMID: 31768712]
[61]
Yamada T, Akamatsu H, Hasegawa S, et al. Age-related changes of p75 Neurotrophin receptor-positive adipose-derived stem cells. J Dermatol Sci 2010; 58(1): 36-42.
[http://dx.doi.org/10.1016/j.jdermsci.2010.02.003] [PMID: 20194005]
[62]
Akamatsu H, Yamada T, Sanada A, et al. Age-related decrease in responsiveness of CD271 positive skin stem cells to growth factors. Exp Dermatol 2022; 31(8): exd.14601..
[http://dx.doi.org/10.1111/exd.14601] [PMID: 35524485]
[63]
Iwata Y, Akamatsu H, Hasegawa S, et al. The epidermal Integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors, while the expression of p75NTR is decreased in patients with chronic skin ulcers. J Dermatol Sci 2013; 71(2): 122-9.
[http://dx.doi.org/10.1016/j.jdermsci.2013.04.006] [PMID: 23642664]
[64]
Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 1986; 83(12): 4167-71.
[http://dx.doi.org/10.1073/pnas.83.12.4167] [PMID: 2424019]
[65]
Galiano RD, Tepper OM, Pelo CR, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 2004; 164(6): 1935-47.
[http://dx.doi.org/10.1016/S0002-9440(10)63754-6] [PMID: 15161630]
[66]
Nauta A, Seidel C, Deveza L, et al. Adipose-derived stromal cells overexpressing vascular endothelial growth factor accelerate mouse excisional wound healing. Mol Ther 2013; 21(2): 445-55.
[http://dx.doi.org/10.1038/mt.2012.234] [PMID: 23164936]
[67]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6): 1194-217.
[http://dx.doi.org/10.1016/j.cell.2013.05.039]
[68]
Quan T, He T, Kang S, Voorhees JJ, Fisher GJ. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signaling. Am J Pathol 2004; 165(3): 741-51.
[http://dx.doi.org/10.1016/S0002-9440(10)63337-8] [PMID: 15331399]
[69]
Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J Clin Invest 2001; 107(2): 135-42.
[http://dx.doi.org/10.1172/JCI11914] [PMID: 11160126]
[70]
Plikus MV, Gay DL, Treffeisen E, Wang A, Supapannachart RJ, Cotsarelis G. Epithelial stem cells and implications for wound repair. Semin Cell Dev Biol 2012; 23(9): 946-53.
[http://dx.doi.org/10.1016/j.semcdb.2012.10.001] [PMID: 23085626]
[71]
Gordon W, Andersen B. A nervous hedgehog rolls into the hair follicle stem cell scene. Cell Stem Cell 2011; 8(5): 459-60.
[http://dx.doi.org/10.1016/j.stem.2011.04.005] [PMID: 21549317]
[72]
Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 1990; 61(7): 1329-37.
[http://dx.doi.org/10.1016/0092-8674(90)90696-C] [PMID: 2364430]
[73]
Horsley V, O’Carroll D, Tooze R, et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell 2006; 126(3): 597-609.
[http://dx.doi.org/10.1016/j.cell.2006.06.048]
[74]
Renault VM, Rafalski VA, Morgan AA, et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 2009; 5(5): 527-39.
[http://dx.doi.org/10.1016/j.stem.2009.09.014]
[75]
Schultz MB, Sinclair DA. When stem cells grow old: Phenotypes and mechanisms of stem cell aging. Development 2016; 143(1): 3-14.
[http://dx.doi.org/10.1242/dev.130633] [PMID: 26732838]

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