吉林大学学报(医学版) ›› 2022, Vol. 48 ›› Issue (1): 256-264.doi: 10.13481/j.1671-587X.20220133
收稿日期:2021-08-17
出版日期:2022-01-28
发布日期:2022-01-17
通讯作者:
李珊山
E-mail:shansalee@163.com
作者简介:谭紫凝(1995-),女,吉林省吉林市人,在读硕士研究生,主要从事白癜风免疫治疗方面的研究。
基金资助:
Received:2021-08-17
Online:2022-01-28
Published:2022-01-17
摘要:
白癜风是一种易诊难治的皮肤疾病,目前临床上尚无特效疗法能有效阻止该病的复发。干细胞是一种具有潜在的无限分裂能力和分化为多种靶细胞能力的细胞,在白癜风的发生发展过程中起重要作用。毛囊中黑素干细胞的增殖和迁移使其成为皮肤中黑素细胞的重要来源和储备。间充质干细胞(骨髓来源和脂肪来源的间充质干细胞)具有免疫调节、抑制氧化应激和促组织修复等功能,可以作为自体黑素细胞移植的辅助治疗。干细胞为白癜风的治疗提供了一个新的可行性方案。目前,国内外学者对干细胞在多种皮肤疾病中临床应用的报道相对较多,但对干细胞在白癜风治疗方面的研究报道较少,且多局限于实验研究阶段,只有少量进入临床试验阶段。现就白癜风的发病机制、干细胞的生物学特性及临床应用优势,以及白癜风相关干细胞进行简要综述,展望其在白癜风治疗中的发展趋势,并对各种干细胞应用可能存在的问题进行评估,旨在为干细胞在白癜风中的应用研究提供参考。
中图分类号:
谭紫凝,甄昱,李珊山. 干细胞与白癜风发生发展的关系及其对白癜风治疗作用的研究进展Research progress in relationship between stem cells and occurrence and development of vitiligo and its therapeutic effect on vitiligo[J]. 吉林大学学报(医学版), 2022, 48(1): 256-264.
| 1 | FRISOLI M L, ESSIEN K, HARRIS J E. Vitiligo: mechanisms of pathogenesis and treatment[J]. Annu Rev Immunol, 2020, 38: 621-648. |
| 2 | NARAYAN V S, UITENTUIS S E, LUITEN R M, et al. Patients’perspective on current treatments and demand for novel treatments in vitiligo[J]. J Eur Acad Dermatol Venereol, 2021, 35(3): 744-748. |
| 3 | NIU C, AISA H A. Upregulation of melanogenesis and tyrosinase activity: potential agents for vitiligo[J]. Molecules, 2017, 22(8): E1303. |
| 4 | CHEN J R, LI S L, LI C Y. Mechanisms of melanocyte death in vitiligo[J]. Med Res Rev, 2021, 41(2): 1138-1166. |
| 5 | BOUKHEDOUNI N, MARTINS C, DARRIGADE A S,et al. Type-1 cytokines regulate MMP-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo[J].JCI Insight,2020,5(11):e133772. |
| 6 | WU X Y, YANG Y W, XIANG L H, et al. The fate of melanocyte: Mechanisms of cell death in vitiligo[J]. Pigment Cell Melanoma Res, 2021, 34(2): 256-267. |
| 7 | BERGQVIST C, EZZEDINE K. Vitiligo: a focus on pathogenesis and its therapeutic implications[J]. J Dermatol, 2021, 48(3): 252-270. |
| 8 | SINGH M, KOTNIS A, JADEJA S D, et al. Cytokines: the Yin and Yang of vitiligo pathogenesis[J]. Expert Rev Clin Immunol, 2019, 15(2): 177-188. |
| 9 | FRĄCZEK A, OWCZARCZYK-SACZONEK A, PLACEK W. The role of TRM cells in the pathogenesis of vitiligo-A review of the current state-of-the-art[J]. Int J Mol Sci, 2020, 21(10): E3552. |
| 10 | SENESCHAL J, BONIFACE K, D’ARINO A, et al. An update on vitiligo pathogenesis[J]. Pigment Cell Melanoma Res, 2021, 34(2): 236-243. |
| 11 | SEARLE T, AL-NIAIMI F, ALI F R. Vitiligo: an update on systemic treatments[J]. Clin Exp Dermatol, 2021, 46(2): 248-258. |
| 12 | LI S L, ZHU G N, YANG Y Q, et al. Oxidative stress drives CD8+ T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes[J]. J Allergy Clin Immunol, 2017, 140(1): 177-189.e9. |
| 13 | ABDALLAH M, EL-MOFTY M, ANBAR T, et al. CXCL-10 and Interleukin-6 are reliable serum markers for vitiligo activity: a multicenter cross-sectional study[J]. Pigment Cell Melanoma Res, 2018, 31(2): 330-336. |
| 14 | RICHMOND J M, STRASSNER J P, RASHIGHI M, et al. Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo[J]. J Invest Dermatol, 2019, 139(4): 769-778. |
| 15 | JAENISCH R, YOUNG R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming[J]. Cell, 2008, 132(4): 567-582. |
| 16 | 黄梁江, 陈 红. 干细胞的临床研究与转化[J]. 内科急危重症杂志, 2020, 26(2): 104-108. |
| 17 | PRAVEEN KUMAR L, KANDOI S, MISRA R,et al. The mesenchymal stem cell secretome: a new paradigm towards cell-free therapeutic mode in regenerative medicine[J]. Cytokine Growth Factor Rev, 2019, 46: 1-9. |
| 18 | BOCHON B, KOZUBSKA M, SURYGAŁA G, et al. Mesenchymal stem cells-potential applications in kidney diseases[J]. Int J Mol Sci, 2019, 20(10): 2462. |
| 19 | OWCZARCZYK-SACZONEK A, WOCIÓR A, PLACEK W, et al. The use of adipose-derived stem cells in selected skin diseases (vitiligo, alopecia, and nonhealing wounds)[J]. Stem Cells Int, 2017, 2017: 4740709. |
| 20 | ZHANG P, KLING R E, RAVURI S K, et al. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration[J]. J Tissue Eng, 2014, 5: 2041731414556850. |
| 21 | ANDERI R, MAKDISSY N, AZAR A, et al. Cellular therapy with human autologous adipose-derived adult cells of stromal vascular fraction for alopecia areata[J]. Stem Cell Res Ther, 2018, 9(1): 141. |
| 22 | PAGANELLI A, KALECI S, BENASSI L, et al. Mesenchymal stem cells and psoriasis: State of the art and future perspectives[J].Dermatol Ther,2020,33(2):e13247. |
| 23 | HEO J R, HWANG K A, KIM S U, et al. A potential therapy using engineered stem cells prevented malignant melanoma in cellular and xenograft mouse models[J]. Cancer Res Treat, 2019, 51(2): 797-811. |
| 24 | CIPRIANI P, DI BENEDETTO P, LIAKOULI V,et al.Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: implications for cellular-based therapy[J]. Clin Exp Immunol, 2013, 173(2): 195-206. |
| 25 | XU J Y. Therapeutic applications of mesenchymal stem cells for systemic lupus erythematosus[J]. Adv Exp Med Biol, 2018, 1089: 73-85. |
| 26 | YANG K, QIU W, GU P R, et al. Regeneration of mouse skin melanocyte stem cells in vivo and in vitro [J]. Methods Mol Biol, 2019, 1879: 267-284. |
| 27 | LI H R, HOU L. Regulation of melanocyte stem cell behavior by the niche microenvironment[J]. Pigment Cell Melanoma Res, 2018, 31(5): 556-569. |
| 28 | LEE J H, FISHER D E. Melanocyte stem cells as potential therapeutics in skin disorders[J]. Expert Opin Biol Ther, 2014, 14(11): 1569-1579. |
| 29 | LEI T C, HEARING V J. Deciphering skin re-pigmentation patterns in vitiligo: an update on the cellular and molecular events involved[J]. Chin Med J (Engl), 2020, 133(10): 1231-1238. |
| 30 | GUO H Y, XING Y Z, LIU Y X, et al. Wnt/β-catenin signaling pathway activates melanocyte stem cells in vitro and in vivo [J]. J Dermatol Sci, 2016, 83(1): 45-51. |
| 31 | INFARINATO N R, STEWART K S, YANG Y H, et al. BMP signaling: at the gate between activated melanocyte stem cells and differentiation[J]. Genes Dev, 2020, 34(23/24): 1713-1734. |
| 32 | REGAZZETTI C, JOLY F, MARTY C, et al. Transcriptional analysis of vitiligo skin reveals the alteration of WNT pathway: a promising target for repigmenting vitiligo patients[J]. J Invest Dermatol, 2015, 135(12): 3105-3114. |
| 33 | YARDMAN-FRANK J M, FISHER D E. Skin pigmentation and its control: From ultraviolet radiation to stem cells[J]. Exp Dermatol, 2021, 30(4): 560-571. |
| 34 | OCAMPO-GARZA J, SALINAS-SANTANDER M, WELSH O, et al. Expression of melanocortin 1 receptor before and after narrowband UVB phototherapy treatment in patients with stable vitiligo: a prospective study[J]. Exp Ther Med, 2020, 19(3): 1649-1654. |
| 35 | BIRLEA S A, GOLDSTEIN N B, NORRIS D A. Repigmentation through melanocyte regeneration in vitiligo[J]. Dermatol Clin, 2017, 35(2): 205-218. |
| 36 | OKAMOTO N, AOTO T, UHARA H, et al. A melanocyte: melanoma precursor niche in sweat glands of volar skin[J]. Pigment Cell Melanoma Res, 2014, 27(6): 1039-1050. |
| 37 | FRIEDENSTEIN A J. Precursor cells of mechanocytes[M]//International review of cytology. Amsterdam: Elsevier, 1976: 327-359. |
| 38 | KESHTKAR S, AZARPIRA N, GHAHREMANI M H. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine[J]. Stem Cell Res Ther, 2018, 9(1): 63. |
| 39 | MEI X Y, SUN Y, WU Z W, et al. In vitro -induced differentiation of bone marrow mesenchymal stem cells into melanocytes[J]. Cell Biol Int, 2015, 39(7): 824-833. |
| 40 | ESQUIVEL D, MISHRA R, SRIVASTAVA A. Stem cell therapy offers a possible safe and promising alternative approach for treating vitiligo: a review[J]. Curr Pharm Des, 2020, 26(37): 4815-4821. |
| 41 | KIM D S, JANG I K, LEE M W, et al. Enhanced immunosuppressive properties of human mesenchymal stem cells primed by interferon-Γ[J]. EBioMedicine, 2018, 28: 261-273. |
| 42 | LANZA C, MORANDO S, VOCI A, et al. Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo [J]. J Neurochem, 2009, 110(5): 1674-1684. |
| 43 | ZHANG F, PENG W X, ZHANG J, et al. New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning[J]. J Cell Biochem, 2019, 120(12): 19902-19914. |
| 44 | ZHU L F, LIN X, ZHI L, et al. Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo[J]. Stem Cell Res Ther, 2020, 11(1): 26. |
| 45 | ZUK P A, ZHU M, MIZUNO H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies[J]. Tissue Eng, 2001, 7(2): 211-228. |
| 46 | MAZINI L, ROCHETTE L, HAMDAN Y, et al. Skin immunomodulation during regeneration: emerging new targets[J]. J Pers Med, 2021, 11(2): 85. |
| 47 | HORINOUCHI C D, BARISÓN M J, ROBERT A W, et al. Influence of donor age on the differentiation and division capacity of human adipose-derived stem cells[J]. World J Stem Cells, 2020, 12(12): 1640-1651. |
| 48 | ZAVALA G, SANDOVAL C, MEZA D, et al. Differentiation of adipose-derived stem cells to functional CD105neg CD73low melanocyte precursors guided by defined culture condition[J]. Stem Cell Res Ther, 2019, 10(1): 249. |
| 49 | GENTILE P, GARCOVICH S. Adipose-derived mesenchymal stem cells (AD-MSCs) against ultraviolet (UV) radiation effects and the skin photoaging[J]. Biomedicines, 2021, 9(5): 532. |
| 50 | EL-BADAWY A, AMER M, ABDELBASET R,et al. Adipose stem cells display higher regenerative capacities and more adaptable electro-kinetic properties compared to bone marrow-derived mesenchymal stromal cells[J]. Sci Rep, 2016, 6: 37801. |
| 51 | KIM J Y, PARK C D, LEE J H, et al. Co-culture of melanocytes with adipose-derived stem cells as a potential substitute for co-culture with keratinocytes[J]. Acta Derm Venereol, 2012, 92(1): 16-23. |
| 52 |
SALEH A A, ABDEL SALAM O H, METWALLY H G, et al. Comparison treatment of vitiligo by co-culture of melanocytes derived from hair follicle with adipose-derived stem cells with and without NB-UVB[J]. Pigmentary Disorders, 2017, 4(1). DOI:10.4172/2376-0427.1000256 .
doi: 10.4172/2376-0427.1000256 |
| 53 | VIZOSO F J, EIRO N, CID S, et al. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine[J]. Int J Mol Sci, 2017, 18(9): E1852. |
| 54 | CHOI E W, SEO M K, WOO E Y, et al. Exosomes from human adipose-derived stem cells promote proliferation and migration of skin fibroblasts[J]. Exp Dermatol, 2018, 27(10): 1170-1172. |
| 55 | XU R, GREENING D W, ZHU H J, et al. Extracellular vesicle isolation and characterization:toward clinical application[J].Clin Invest,2016,126(4):1152-1162. |
| 56 | BELLEI B, MIGLIANO E, TEDESCO M, et al. Adipose tissue-derived extracellular fraction characterization: biological and clinical considerations in regenerative medicine[J]. Stem Cell Res Ther, 2018, 9(1): 207. |
| 57 | CAI Y, LI J Y, JIA C S, et al. Therapeutic applications of adipose cell-free derivatives: a review[J]. Stem Cell Res Ther, 2020, 11(1): 312. |
| 58 | BELLEI B, PAPACCIO F, FILONI A, et al. Extracellular fraction of adipose tissue as an innovative regenerative approach for vitiligo treatment[J]. Exp Dermatol, 2019, 28(6): 695-703. |
| 59 | PAINO F, RICCI G, DE ROSA A, et al. Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes[J]. Eur Cell Mater, 2010, 20: 295-305. |
| 60 | TSUCHIYAMA K, WAKAO S, KURODA Y, et al. Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts[J]. J Invest Dermatol, 2013, 133(10): 2425-2435. |
| 61 | YAMAUCHI T, YAMASAKI K, TSUCHIYAMA K, et al. A quantitative analysis of multilineage-differentiating stress-enduring (Muse) cells in human adipose tissue and efficacy of melanocytes induction[J]. J Dermatol Sci, 2017, 86(3): 198-205. |
| 62 | FANG D, LEISHEAR K, NGUYEN T K, et al. Defining the conditions for the generation of melanocytes from human embryonic stem cells[J]. Stem Cells, 2006, 24(7): 1668-1677. |
| 63 | WU D C, BOYD A S, WOOD K J. Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine[J]. Front Biosci, 2007, 12: 4525-4535. |
| 64 | GLEDHILL K, GUO Z Y, UMEGAKI-ARAO N,et al. Melanin transfer in human 3D skin equivalents generated exclusively from induced pluripotent stem cells[J]. PLoS One, 2015, 10(8): e0136713. |
| 65 | 李遇梅, 张怡萱, 刘莉萍. 诱导性多功能干细胞在皮肤科研究与应用的进展[J]. 中华皮肤科杂志, 2019, 52(7): 445-449. |
| 66 | 伍婧玥, 李 敏, 王 刚, 等. 毛囊干细胞的应用领域[J]. 中华细胞与干细胞杂志(电子版), 2020, 10(6): 359-363. |
| 67 | YASHIRO M, MII S, AKI R, et al. From hair to heart: nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells differentiate to beating cardiac muscle cells[J]. Cell Cycle, 2015, 14(14): 2362-2366. |
| 68 | TOTANI A, AMIN H, BACCHI S, et al. Vitiligo following stem-cell transplant[J]. Bone Marrow Transplant, 2020, 55(2): 332-340. |
| 69 | SANLI H, AKAY B N, ARAT M, et al. Vitiligo after hematopoietic cell transplantation: six cases and review of the literature[J]. Dermatology, 2008, 216(4): 349-354. |
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