Gene-activated Matrix/bone Marrow-derived Mesenchymal Stem Cells Constructs Regenerate Sweat Glands-like Structure in Vivo

Overview

Journal Sci Rep

Specialty Science

Date 2017 Dec 17

PMID 29247230

Citations 10

Authors

Pranish Kolakshyapati

Xiuyuan Li

Chunye Chen

Mingxia Zhang

Weiqiang Tan

Lie Ma

Changyou Gao

Affiliations

Soon will be listed here.

Abstract

It is a significant challenge to regenerate full-thickness skin defects with sweat glands. Various skin substitutes have been developed to resolve this issue with minimal success. In this study, to yield a novel construct for in situ regeneration of sweat glands, the collagen-chitosan porous scaffold was combined with Lipofectamine 2000/pDNA-EGF complexes to obtain the gene-activated scaffold (GAS), which was then seeded with bone marrow-derived mesenchymal stem cells (BM-MSCs). The porous scaffold functionalized as a reservoir for the incorporated gene complexes which were released in a sustained manner. The seeded BM-MSCs were transfected in situ by the released complexes and specially differentiated into sweat gland cells in vitro under the induction of the expressed epidermal growth factor (EGF). Application in vivo of the GAS/BM-MSCs constructs on the full-thickness skin defects of SD rats confirmed that GAS/BM-MSCs could accelerate the wound healing process and induce the in situ regeneration of the full-thickness skin with sweat gland-like structures. Analyzed by immunohistochemical staining, RT-qPCR and Western-blotting, the levels of the major sweat gland markers such as carcino-embryonic antigen (CEA), cytokeratin 8 (CK8) and cytokeratin 14 (CK14) were all up-regulated, indicating that GAS/BM-MSCs can facilitate the regeneration of sweat glands-like structure in vivo.

Citing Articles

Advances and applications of biomimetic biomaterials for endogenous skin regeneration.

Wang M, Hong Y, Fu X, Sun X Bioact Mater. 2024; 39:492-520.

PMID: 38883311 PMC: 11179177. DOI: 10.1016/j.bioactmat.2024.04.011.

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration.

Wu S, Sun S, Fu W, Yang Z, Yao H, Zhang Z Biomedicines. 2024; 12(4).

PMID: 38672102 PMC: 11048165. DOI: 10.3390/biomedicines12040743.

Biofabrication of Human Skin with Its Appendages.

Hosseini M, Koehler K, Shafiee A Adv Healthc Mater. 2022; 11(22):e2201626.

PMID: 36063498 PMC: 11469047. DOI: 10.1002/adhm.202201626.

Paeoniflorin inhibits proliferation and promotes autophagy and apoptosis of sweat gland cells.

Xu Y, He H, Li P, Liu H Exp Ther Med. 2021; 23(1):53.

PMID: 34934430 PMC: 8652401. DOI: 10.3892/etm.2021.10975.

Anti-Aging β-Klotho Gene-Activated Scaffold Promotes Rejuvenative Wound Healing Response in Human Adipose-Derived Stem Cells.

Laiva A, OBrien F, Keogh M Pharmaceuticals (Basel). 2021; 14(11).

PMID: 34832950 PMC: 8619173. DOI: 10.3390/ph14111168.

References

Guo R, Xu S, Ma L, Huang A, Gao C . The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen-chitosan dermal equivalents. Biomaterials. 2010; 32(4):1019-31. DOI: 10.1016/j.biomaterials.2010.08.087. View

Shikiji T, Minami M, Inoue T, Hirose K, Oura H, Arase S . Keratinocytes can differentiate into eccrine sweat ducts in vitro: involvement of epidermal growth factor and fetal bovine serum. J Dermatol Sci. 2003; 33(3):141-50. DOI: 10.1016/j.jdermsci.2003.09.004. View

Huang S, Yao B, Xie J, Fu X . 3D bioprinted extracellular matrix mimics facilitate directed differentiation of epithelial progenitors for sweat gland regeneration. Acta Biomater. 2016; 32:170-177. DOI: 10.1016/j.actbio.2015.12.039. View

Tyrone J, Mogford J, Chandler L, Ma C, Xia Y, Pierce G . Collagen-embedded platelet-derived growth factor DNA plasmid promotes wound healing in a dermal ulcer model. J Surg Res. 2000; 93(2):230-6. DOI: 10.1006/jsre.2000.5912. View

Pannier A, Shea L . Controlled release systems for DNA delivery. Mol Ther. 2004; 10(1):19-26. DOI: 10.1016/j.ymthe.2004.03.020. View

Huang S, Lu G, Wu Y, Jirigala E, Xu Y, Ma K . Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair. J Dermatol Sci. 2012; 66(1):29-36. DOI: 10.1016/j.jdermsci.2012.02.002. View

Xu Y, Huang S, Ma K, Fu X, Han W, Sheng Z . Promising new potential for mesenchymal stem cells derived from human umbilical cord Wharton's jelly: sweat gland cell-like differentiative capacity. J Tissue Eng Regen Med. 2011; 6(8):645-54. DOI: 10.1002/term.468. View

Li H, Li X, Zhang M, Chen L, Zhang B, Tang S . Three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes transdifferentiation of BM-MSCs. J Mol Histol. 2015; 46(4-5):431-8. DOI: 10.1007/s10735-015-9632-5. View

Fu X, Qu Z, Sheng Z . Potentiality of mesenchymal stem cells in regeneration of sweat glands. J Surg Res. 2006; 136(2):204-8. DOI: 10.1016/j.jss.2005.03.024. View

10.

Takeo M, Lee W, Ito M . Wound healing and skin regeneration. Cold Spring Harb Perspect Med. 2015; 5(1):a023267. PMC: 4292081. DOI: 10.1101/cshperspect.a023267. View

11.

Zhao Z, Xu M, Wu M, Ma K, Sun M, Tian X . Direct reprogramming of human fibroblasts into sweat gland-like cells. Cell Cycle. 2015; 14(21):3498-505. PMC: 4825576. DOI: 10.1080/15384101.2015.1093707. View

12.

Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S . Bone regeneration by modified gene-activated matrix: effectiveness in segmental tibial defects in rats. Tissue Eng. 2006; 12(3):489-97. DOI: 10.1089/ten.2006.12.489. View

13.

Beumer G, van Blitterswijk C, Bakker D, Ponec M . Cell-seeding and in vitro biocompatibility evaluation of polymeric matrices of PEO/PBT copolymers and PLLA. Biomaterials. 1993; 14(8):598-604. DOI: 10.1016/0142-9612(93)90178-5. View

14.

Banyard D, Bourgeois J, Widgerow A, Evans G . Regenerative biomaterials: a review. Plast Reconstr Surg. 2015; 135(6):1740-1748. DOI: 10.1097/PRS.0000000000001272. View

15.

Xu Y, Hong Y, Xu M, Ma K, Fu X, Zhang M . Role of Keratinocyte Growth Factor in the Differentiation of Sweat Gland-Like Cells From Human Umbilical Cord-Derived Mesenchymal Stem Cells. Stem Cells Transl Med. 2015; 5(1):106-16. PMC: 4704873. DOI: 10.5966/sctm.2015-0081. View

16.

Blecher S, Kapalanga J, Lalonde D . Induction of sweat glands by epidermal growth factor in murine X-linked anhidrotic ectodermal dysplasia. Nature. 1990; 345(6275):542-4. DOI: 10.1038/345542a0. View

17.

Buchanan P, Kung T, Cederna P . Evidence-based medicine: Wound closure. Plast Reconstr Surg. 2014; 134(6):1391-1404. DOI: 10.1097/PRS.0000000000000720. View

18.

Hijjawi J, Mogford J, Chandler L, Cross K, Said H, Sosnowski B . Platelet-derived growth factor B, but not fibroblast growth factor 2, plasmid DNA improves survival of ischemic myocutaneous flaps. Arch Surg. 2004; 139(2):142-7. DOI: 10.1001/archsurg.139.2.142. View

19.

Harris P, Di Francesco F, Barisoni D, Leigh I, Navsaria H . Use of hyaluronic acid and cultured autologous keratinocytes and fibroblasts in extensive burns. Lancet. 1999; 353(9146):35-6. DOI: 10.1016/s0140-6736(05)74873-x. View

20.

Jiang P, Mao Z, Gao C . Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells. Acta Biomater. 2015; 19:76-84. DOI: 10.1016/j.actbio.2015.03.018. View