Full-thickness tissue engineered skin constructed with autogenic bone marrow mesenchymal stem cells (original) (raw)
Abstract
To explore the feasibility of repairing clinical cutaneous deficiency, autogenic bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into epidermal cells and fibroblasts in vitro supplemented with different inducing factors and biomaterials to construct functional tissueengineered skin. The results showed that after 72 h induction, BMSCs displayed morphologic changes such as typical epidermal cell arrangement, from spindle shape to round or oval; tonofibrils, melanosomes and keratohyaline granules were observed under a transmission electronic microscope. The differentiated cells expressed epidermal stem cell surface marker CK19 (59.66% ± 4.2%) and epidermal cells differentiation marker CK10. In addition, the induced epidermal cells acquired the anti-radiation capacity featured by lowered apoptosis following exposure to UVB. On the other hand, the collagen microfibrils deposition was noticed under a transmission electronic microscope after differentiating into dermis fibroblasts; RT-PCR identified collagen type I mRNA expression in differentiated cells; radioimmunoassay detected the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) (up to 115.06 pg/mL and 0.84 ng/mL, respectively). Further in vivo implanting BMSCs with scaffold material shortened skin wound repair significantly. In one word, autogenic BMSCs have the potential to differentiate into epidermal cells and fibroblasts in vitro, and show clinical feasibility acting as epidermis-like and dermis-like seed cells in skin engineering.
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References
- Pittenger M F, Mackay A M, Beek S C, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284: 143–147
Article PubMed CAS Google Scholar - Robert J D, Annemarie B M. Mesenchymal stem cells: Biology and potential clinical uses. Exp Hemato, 2000, 28: 875–884
Article Google Scholar - David J A, Fred H G, Irving L W. Can stem cells cross the lineage boundaries? Nat Med, 2001, 7: 393–395
Article Google Scholar - Timothy R B, Fabio MVR, Gilmor L K, et al. From marrow to brain: Expression of neuronal phenotypes in adult mice. Science, 2000, 290: 1775–1779
Article Google Scholar - Nakagawa H, Akita S, Fukui M, et al. Human mesenchymal stem cells successfully improve skin-substitute wound healing. Br J Dermatol, 2005, 153: 29–36
Article PubMed CAS Google Scholar - Fang L J, Fu X B, Sun T Z, et al. The initial observation of differentiation into epidermal cells in vivo of human bone marrow mesenchymal stem cells. Chinese J Traumatol, 2003, 19: 212–214
Google Scholar - Hou L L, Cao H, Bai C X, et al. The experimental research of proliferation and differentiation into nerve cells in vitro of human bone marrow mesenchymal stem cells. Chin Sci Bull, 2002, 47: 277–281
Google Scholar - Kulms D, Zcisc E. DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene, 2002, 21: 5844–5851
Article PubMed CAS Google Scholar - Kulms D, Schwarz T. Independent contribution of three different pathways to ultraviolet-B-induced apoptosis. Biochem Pharmacol, 2002, 64: 837–841
Article PubMed CAS Google Scholar - Assefaa Z, Van Laethem A, Garmyn M, et al. Ultraviolet radiation-induced apoptosis in keratinocytes: On the role of cytosolic factors. Biochim Biophys Acta, 2005, 1755: 90–106
Google Scholar - Canguihem B, Pradines A, Baudouin C, et al. RhoB Protects human keratinocytes from UVB-induced apoptosis through epidermal growth factor receptor signaling. J Biol Chem, 2005, 280: 43257–43263
Article Google Scholar - Kuhn C, Hurwitz S A. Activation of the insulin-like growth factor-1 receptor promotes the survival of human keratinocytes following ultraviolet B irradiation. Int J Cancer, 1999, 80: 431–438
Article PubMed CAS Google Scholar - Decraene D, Agostinis P, Bouillon R, et al. Insulin-like growth factor-1-mediated AKT activation postopones the onset of ultraviolet B-induced apoptosis, providing more time for cyclobutane thymine dimer removal in primary human keratinocytes. J Biol Chem, 2002, 277:32587–32595
Article PubMed CAS Google Scholar - Cheng J, Grande J P. Transforming growth factor beta signal transduction and progressive renal disease. Exp Biol Med, 2002, 227: 943–956
CAS Google Scholar - Mori Y, Chen S J, Varga J. Modulation of endogenous Smad expression in normal skin fibroblasts by transforming growth factor. Exp Cell Res, 2000, 258: 374–383
Article PubMed CAS Google Scholar - Masatoshi J, Hironobu I. α2(I) collagen gene regulation by protein kinase C signaling in human dermal fibroblasts. Nucleic Acids Research, 2005, 33: 1337–1351
Article Google Scholar - Lin Z Q, Kondo T, Ishida Y, et al. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol, 2003, 73: 713–721
Article PubMed CAS Google Scholar - Gallucci R M, Sloan D K, IIeck J M, et al. Interleukin 6 indirectly induces keratinocyte migration. J Invest Dermatol, 2004, 122: 764–772
Article PubMed CAS Google Scholar - Wang X P, Schunck M, Kallen K J, et al. The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. J Invest Dermatol, 2004, 123: 124–131
Article PubMed CAS Google Scholar - Mackenzie T C, Flake A W. Human mesenchymal stem cells persist demonstrate site-specific multipotential differentiation and are present in sites of wound healing and tissue regeneration after transplantation into fetal sheep. Blood Cells Mol Dis, 2001, 27: 601–604
Article PubMed CAS Google Scholar
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Authors and Affiliations
- Laboratory of Stem Cells and Regenerative Medicine, Institute of Blood Transfusion, Academy of Military Medical Sciences, Beijing, 100850, China
He LiJuan, Nan Xue, Wang YunFang, Guan LiDong, Bai CiXian, Shi ShuangShuang, Yuan HongFeng, Chen Lin, Liu DaQing & Pei XueTao
Authors
- He LiJuan
- Nan Xue
- Wang YunFang
- Guan LiDong
- Bai CiXian
- Shi ShuangShuang
- Yuan HongFeng
- Chen Lin
- Liu DaQing
- Pei XueTao
Corresponding author
Correspondence toPei XueTao.
Additional information
Supported by the Major Technology Program of Beijing Municipal Science & Technology Commission (Grant No. H060920050130) and the Major State Basic Research Development Program of China (Grant No. 2005CB522702)
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He, L., Nan, X., Wang, Y. et al. Full-thickness tissue engineered skin constructed with autogenic bone marrow mesenchymal stem cells.SCI CHINA SER C 50, 429–437 (2007). https://doi.org/10.1007/s11427-007-0069-2
- Received: 26 December 2006
- Accepted: 13 April 2007
- Issue date: August 2007
- DOI: https://doi.org/10.1007/s11427-007-0069-2