Human hair follicle stem cell differentiation into contractile smooth muscle cells is induced by transforming growth factor-β1 and platelet-derived growth factor BB

Xu,Zhi  Cheng; Zhang,Qun; Li,Hong

doi:10.3892/mmr.2013.1707

Human hair follicle stem cell differentiation into contractile smooth muscle cells is induced by transforming growth factor-β1 and platelet-derived growth factor BB

Authors:
- Zhi Cheng Xu
- Qun Zhang
- Hong Li
View Affiliations

Affiliations: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, P.R. China, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai, P.R. China
Published online on: September 27, 2013 https://doi.org/10.3892/mmr.2013.1707
Pages: 1715-1721

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Smooth muscle cells (SMCs) are important in vascular homeostasis and disease and thus, are critical elements in vascular tissue engineering. Although adult SMCs have been used as seed cells, such mature differentiated cells suffer from limited proliferation potential and cultural senescence, particularly when originating from older donors. By comparison, human hair follicle stem cells (hHFSCs) are a reliable source of stem cells with multi‑differentiation potential. The aim of the present study, was to develop an efficient strategy to derive functional SMCs from hHFSCs. hHFSCs were obtained from scalp tissues of healthy adult patients undergoing cosmetic plastic surgery. The hHFSCs were expanded to passage 2 and induced by the administration of transforming growth factor‑β1 (TGF‑β1) and platelet‑derived growth factor BB (PDGF‑BB) in combination with culture medium. Expression levels of SMC‑related markers, including α‑smooth muscle actin (α‑SMA), α‑calponin and smooth muscle myosin heavy chain (SM‑MHC), were detected by immunofluorescence staining, flow cytometry analysis and reverse transcription-polymerase chain reaction (RT‑PCR). When exposed to differentiation medium, hHFSCs expressed early, mid and late markers (α‑SMA, α‑calponin and SM‑MHC, respectively) that were similar to the markers expressed by human umbilical artery SMCs. Notably, when entrapped inside a collagen matrix lattice, these SM differentiated cells showed a contractile function. Therefore, the present study developed an efficient strategy for differentiating hHFSCs into contractile SMCs by stimulation with TGF‑β1 and PDGF‑BB. The high yield of derivation suggests that this strategy facilitates the acquisition of the large numbers of cells that are required for blood vessel engineering and the study of vascular disease pathophysiology.

View Figures

View References

1	Owens GK, Kumar MS and Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 84:767–801. 2004. View Article : Google Scholar : PubMed/NCBI
2	Sundaram S and Niklason LE: Smooth muscle and other cell sources for human blood vessel engineering. Cells Tissues Organs. 195:15–25. 2012.PubMed/NCBI
3	Xu ZC, Zhang WJ, Li H, Cui L, Cen L, Zhou GD, Liu W and Cao Y: Engineering of an elastic large muscular vessel wall with pulsatile stimulation in bioreactor. Biomaterials. 29:1464–1472. 2008. View Article : Google Scholar : PubMed/NCBI
4	Poh M, Boyer M, Solan A, Dahl SL, Pedrotty D, Banik SS, McKee JA, Klinger RY, Counter CM and Niklason LE: Blood vessels engineered from human cells. Lancet. 365:2122–2124. 2005. View Article : Google Scholar : PubMed/NCBI
5	McKee JA, Banik SS, Boyer MJ, Hamad NM, Lawson JH, Niklason LE and Counter CM: Human arteries engineered in vitro. EMBO Rep. 4:633–638. 2003. View Article : Google Scholar : PubMed/NCBI
6	Bajpai VK and Andreadis ST: Stem cell sources for vascular tissue engineering and regeneration. Tissue Eng Part B Rev. 18:405–425. 2012.PubMed/NCBI
7	Matsumura G, Miyagawa-Tomita S, Shin’oka T, Ikada Y and Kurosawa H: First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo. Circulation. 108:1729–1934. 2003. View Article : Google Scholar : PubMed/NCBI
8	Shin’oka T, Matsumura G, Hibino N, Naito Y, Watanabe M, Konuma T, Sakamoto T, Nagatsu M and Kurosawa H: Midterm clinical result of tissue-engineered vascular autografts seeded with autologous bone marrow cells. J Thorac Cardiovasc Surg. 129:1330–1338. 2005.
9	Gong Z and Niklason LE: Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs). FASEB J. 22:1635–1648. 2008. View Article : Google Scholar
10	Heydarkhan-Hagvall S, Schenke-Layland K, Yang JQ, Heydarkhan S, Xu Y, Zuk PA, MacLellan WR and Beygui RE: Human adipose stem cells: a potential cell source for cardiovascular tissue engineering. Cells Tissues Organs. 187:263–274. 2008.PubMed/NCBI
11	Wang C, Cen L, Yin S, Liu Q, Liu W, Cao Y and Cui L: A small diameter elastic blood vessel wall prepared under pulsatile conditions from polyglycolic acid mesh and smooth muscle cells differentiated from adipose-derived stem cells. Biomaterials. 31:621–630. 2010. View Article : Google Scholar
12	Harris LJ, Abdollahi H, Zhang P, McIlhenny S, Tulenko TN and DiMuzio PJ: Differentiation of adult stem cells into smooth muscle for vascular tissue engineering. J Surg Res. 168:306–314. 2011. View Article : Google Scholar : PubMed/NCBI
13	Hsu YC, Pasolli HA and Fuchs E: Dynamics between stem cells, niche, and progeny in the hair follicle. Cell. 144:92–105. 2011. View Article : Google Scholar : PubMed/NCBI
14	Mistriotis P and Andreadis ST: Hair Follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 19:265–278. 2013.PubMed/NCBI
15	Jahoda CA, Whitehouse J, Reynolds AJ and Hole N: Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages. Exp Dermatol. 12:849–859. 2003. View Article : Google Scholar : PubMed/NCBI
16	Yu H, Fang D, Kumar SM, Li L, Nguyen TK, Acs G, Herlyn M and Xu X: Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol. 168:1879–1888. 2006. View Article : Google Scholar : PubMed/NCBI
17	Drewa T, Joachimiak R, Kaznica A, Sarafian V and Pokrywczynska M: Hair stem cells for bladder regeneration in rats: preliminary results. Transplant Proc. 41:4345–4351. 2009. View Article : Google Scholar : PubMed/NCBI
18	Lin H, Liu F, Zhang C, Zhang Z, Kong Z, Zhang X and Hoffman RM: Characterization of nerve conduits seeded with neurons and Schwann cells derived from hair follicle neural crest stem cells. Tissue Eng Part A. 17:1691–1698. 2011. View Article : Google Scholar : PubMed/NCBI
19	Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S and Akhurst RJ: Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development. 121:1845–1854. 1995.PubMed/NCBI
20	Shah NM, Groves AK and Anderson DJ: Alternative neural crest cell fates are instructively promoted by TGFbeta superfamily members. Cell. 85:331–343. 1996. View Article : Google Scholar : PubMed/NCBI
21	Grainger DJ, Metcalfe JC, Grace AA and Mosedale DE: Transforming growth factor-beta dynamically regulates vascular smooth muscle differentiation in vivo. J Cell Sci. 111:2977–2988. 1998.PubMed/NCBI
22	Hirschi KK, Rohovsky SA and D’Amore PA: PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol. 141:805–814. 1998. View Article : Google Scholar : PubMed/NCBI
23	Chen S and Lechleider RJ: Transforming growth factor-beta-induced differentiation of smooth muscle from a neural crest stem cell line. Circ Res. 94:1195–1202. 2004. View Article : Google Scholar : PubMed/NCBI
24	Hirschi KK, Burt JM, Hirschi KD and Dai C: Gap junction communication mediates transforming growth factor-beta activation and endothelial-induced mural cell differentiation. Circ Res. 93:429–437. 2003. View Article : Google Scholar : PubMed/NCBI
25	Ross JJ, Hong Z, Willenbring B, Zeng L, Isenberg B, Lee EH, Reyes M, Keirstead SA, Weir EK, Tranquillo RT and Verfaillie CM: Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells. J Clin Invest. 116:3139–3149. 2006. View Article : Google Scholar : PubMed/NCBI
26	Lindahl P, Johansson BR, Levéen P and Betsholtz C: Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 277:242–245. 1997. View Article : Google Scholar : PubMed/NCBI
27	Hellström M, Kalén M, Lindahl P, Abramsson A and Betsholtz C: Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 126:3047–3055. 1999.PubMed/NCBI
28	Kim YM, Jeon ES, Kim MR, Jho SK, Ryu SW and Kim JH: Angiotensin II-induced differentiation of adipose tissue-derived mesenchymal stem cells to smooth muscle-like cells. Int J Biochem Cell Biol. 40:2482–2491. 2008. View Article : Google Scholar : PubMed/NCBI
29	McKee JA, Banik SS, Boyer MJ, Hamad NM, Lawson JH, Niklason LE and Counter CM: Human arteries engineered in vitro. EMBO Rep. 4:633–638. 2003. View Article : Google Scholar : PubMed/NCBI
30	Long JL and Tranquillo RT: Elastic fiber production in cardiovascular tissue-equivalents. Matrix Biol. 22:339–350. 2003. View Article : Google Scholar : PubMed/NCBI
31	Gong Z and Niklason LE: Blood vessels engineered from human cells. Trends Cardiovasc Med. 16:153–156. 2006. View Article : Google Scholar : PubMed/NCBI
32	Isenberg BC, Williams C and Tranquillo RT: Small-diameter artificial arteries engineered in vitro. Circ Res. 98:25–35. 2006. View Article : Google Scholar : PubMed/NCBI
33	Cho SW, Lim SH, Kim IK, Hong YS, Kim SS, Yoo KJ, Park HY, Jang Y, Chang BC, Choi CY, et al: Small-diameter blood vessels engineered with bone marrow-derived cells. Ann Surg. 241:506–515. 2005. View Article : Google Scholar : PubMed/NCBI
34	Rodríguez LV, Alfonso Z, Zhang R, Leung J, Wu B and Ignarro LJ: Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc Natl Acad Sci USA. 103:12167–12172. 2006.PubMed/NCBI
35	Beltrami AP, Cesselli D, Bergamin N, Marcon P, Rigo S, Puppato E, D’Aurizio F, Verardo R, Piazza S, Pignatelli A, et al: Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood. 110:3438–3446. 2007. View Article : Google Scholar : PubMed/NCBI
36	Miano JM: Mammalian smooth muscle differentiation: origins, markers and transcriptional control. Results Probl Cell Differ. 38:39–59. 2002. View Article : Google Scholar : PubMed/NCBI
37	Grainger DJ: Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis. Arterioscler Thromb Vasc Biol. 24:399–404. 2004. View Article : Google Scholar : PubMed/NCBI
38	Björkerud S: Effects of transforming growth factor-beta 1 on human arterial smooth muscle cells in vitro. Arterioscler Thromb. 11:892–902. 1991.PubMed/NCBI
39	Deaton RA, Su C, Valencia TG and Grant SR: Transforming growth factor-beta 1-induced expression of smooth muscle marker genes involves activation of PKN and p38 MAPK. J Biol Chem. 280:31172–31181. 2005. View Article : Google Scholar : PubMed/NCBI
40	Hautmann MB, Madsen CS and Owens GK: A transforming growth factor beta (TGFbeta) control element drives TGFbeta-induced stimulation of smooth muscle alpha-actin gene expression in concert with two CarG elements. J Biol Chem. 272:10948–10956. 1997. View Article : Google Scholar
41	Kawai-Kowase K, Sato H, Oyama Y, Kanai H, Sato M, Doi H and Kurabayashi M: Basic fibroblast growth factor antagonizes transforming growth factor-beta1-induced smooth muscle gene expression through extracellular signal-regulated kinase 1/2 signaling pathway activation. Arterioscler Thromb Vasc Biol. 24:1384–1390. 2004. View Article : Google Scholar
42	Papetti M, Shujath J, Riley KN and Herman IM: FGF-2 antagonizes the TGF-beta1-mediated induction of pericyte alpha-smooth muscle actin expression: a role for myf-5 and Smad-mediated signaling pathways. Invest Ophthalmol Vis Sci. 44:4994–5005. 2003. View Article : Google Scholar : PubMed/NCBI
43	Kucich U, Rosenbloom JC, Abrams WR, Bashir MM and Rosenbloom J: Stabilization of elastin mRNA by TGF-beta: initial characterization of signaling pathway. Am J Respir Cell Mol Biol. 17:10–16. 1997. View Article : Google Scholar : PubMed/NCBI
44	Kucich U, Rosenbloom JC, Abrams WR and Rosenbloom J: Transforming growth factor-beta stabilizes elastin mRNA by a pathway requiring active Smads, protein kinase C-delta, and p38. Am J Respir Cell Mol Biol. 26:183–188. 2002. View Article : Google Scholar : PubMed/NCBI
45	Hong HH, Uzel MI, Duan C, Sheff MC and Trackman PC: Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva. Lab Invest. 79:1655–1667. 1999.PubMed/NCBI
46	Ross JJ and Tranquillo RT: ECM gene expression correlates with in vitro tissue growth and development in fibrin gel remodeled by neonatal smooth muscle cells. Matrix Biol. 22:477–490. 2003. View Article : Google Scholar : PubMed/NCBI
47	Yao L, Swartz DD, Gugino SF, Russell JA and Andreadis ST: Fibrin-based tissue-engineered blood vessels: differential effects of biomaterial and culture parameters on mechanical strength and vascular reactivity. Tissue Eng. 11:991–1003. 2005. View Article : Google Scholar
48	Sinha S, Hoofnagle MH, Kingston PA, McCanna ME and Owens GK: Transforming growth factor-beta1 signaling contributes to development of smooth muscle cells from embryonic stem cells. Am J Physiol Cell Physiol. 287:C1560–C1568. 2004. View Article : Google Scholar : PubMed/NCBI
49	Kinner B, Zaleskas JM and Spector M: Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells. Exp Cell Res. 278:72–83. 2002. View Article : Google Scholar : PubMed/NCBI
50	Wang D, Park JS, Chu JS, Krakowski A, Luo K, Chen DJ and Li S: Proteomic profiling of bone marrow mesenchymal stem cells upon transforming growth factor beta1 stimulation. J Biol Chem. 279:43725–43734. 2004. View Article : Google Scholar : PubMed/NCBI
51	Collins T, Pober JS, Grimbone MA Jr, Hammacher A, Betsholtz C, Westermark B and Heldin CH: Cultured human endothelial cells express platelet-derived growth factor A chain. Am J Pathol. 126:7–12. 1987.PubMed/NCBI
52	Westermark B, Siegbahn A, Heldin CH and Claesson-Welsh L: B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase. Proc Natl Acad Sci USA. 87:128–132. 1990. View Article : Google Scholar
53	Holmgren L, Glaser A, Pfeifer-Ohlsson S and Ohlsson R: Angiogenesis during human extraembryonic development involves the spatiotemporal control of PDGF ligand and receptor gene expression. Development. 113:749–754. 1991.PubMed/NCBI
54	Hyytiäinen M, Penttinen C and Keski-Oja J: Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Crit Rev Clin Lab Sci. 41:233–264. 2004.PubMed/NCBI
55	Derynck R and Akhurst RJ: Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol. 9:1000–1004. 2007. View Article : Google Scholar : PubMed/NCBI
56	Liang MS and Andreadis ST: Engineering fibrin-binding TGF-β1 for sustained signaling and contractile function of MSC based vascular constructs. Biomaterials. 32:8684–8693. 2011.PubMed/NCBI
57	Gallagher JT: Heparan sulfate: growth control with a restricted menu. J Clin Invest. 108:357–361. 2001. View Article : Google Scholar : PubMed/NCBI