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Induction of corneal epithelial progenitors from bone-marrow mesenchymal stem cells of rhesus monkeys in vitro

  • Articles
  • Cell Biology
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Chinese Science Bulletin

Abstract

Bioengineered corneas are substitutes for human donor tissue that are designed to treat severe disease affecting ocular surfaces. However, a shortage of candidate seed cells for bioengineering corneas is still a problem. Bone-marrow mesenchymal stem cells (MSCs) are capable of multilineage differentiation. Therefore, we determined whether MSCs differentiate into corneal epithelial cells (ECs). We applied three exoteric-microenvironmental systems to induce MSCs to become ECs. Induced MSC were identified by means of morphologic examination, immunocytochemical analysis, and flow cytometry. MSCs grown in one microenvironment had characteristics similar to those of corneal epithelial progenitors. Induced MSCs expressed markers for EC, including integrin β1, Cx43, Pax6, and P63. MSCs were successfully induced to become corneal epithelial progenitors. Therefore, the use of MSCs may hold substantial promise for reconstructing the ocular surface after corneal injury.

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References

  1. Morgan S, Murray A. Limbal autotransplantation in the acute and chronic phases of severe chemical injuries. Eye, 1996, 10(Pt 3): 349–354

    Google Scholar 

  2. Pellegrini G, Traverso C E, Franzi A T, et al. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Larnet, 1997, 49(9057): 990–993

    Google Scholar 

  3. Tsubota K, Satake Y, Kaido M, et al. Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med, 1999, 340(22): 1697–1703

    Article  Google Scholar 

  4. Holland E J, Schwartz G S. Epithelial stem cell transplantation for severe ocular surface disease. N Engl J Med, 1999, 340(22): 1752–1753

    Article  Google Scholar 

  5. Tsai R J, Li L M, Chen J K. Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med, 2000, 343(2): 86–93

    Article  Google Scholar 

  6. Li Q J, Ashraf F M, Rana T S, et al. Long-term survival of allogeneic donor cell-derived corneal epithelium in limbal deficient rabbits. Curr Eye Res, 2001, 23(5): 336–345

    Article  Google Scholar 

  7. Solomon A, Ellies P, Anderson D F, et al. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology, 2002, 109(6): 1159–1166

    Article  Google Scholar 

  8. Reinhard T, Spelsberg H, Henke L, et al. Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency. Ophthalmology, 2004, 111(4): 775–782

    Article  Google Scholar 

  9. Sharpe J R, Daya S M, Dimitriadi M, et al. Survival of cultured allogeneic limbal epithelial cells following corneal repair. Tissue Eng, 2007, 13(1): 123–132

    Article  Google Scholar 

  10. Nakamura T, Endo K, Cooper L J, et al. The successful culture and autologous transplantation of rabbit oral mucosal epithelial cells on amniotic membrane. Invest Ophthalmol Vis Sci, 2003, 44(1): 106–116

    Article  Google Scholar 

  11. Lumelsky N, Blondel O, Laeng P, et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 2001, 292(5520): 1389–1394

    Article  Google Scholar 

  12. Zhang S C, Wernig M, Duncan I D, et al. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol, 2001, 19(12): 1129–1133

    Article  Google Scholar 

  13. Chinzei R, Tanaka Y, Shimizu-Saito K, et al. Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology, 2002, 36(1): 22–29

    Article  Google Scholar 

  14. Ali N N, Edgar A J, Samadikuchaksaraei A, et al. Derivation of type II alveolar epithelial cells from murine embryonic stem cells. Tissue Eng, 2002, 8: 541–550

    Article  Google Scholar 

  15. Kawasaki H, Suemori H, Mizuseki K, et al. Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA, 2002, 99(3): 1580–1585

    Article  Google Scholar 

  16. Chiba S, Iwasaki Y, Sekino H, et al. Transplantation of motoneuron-enriched neural cells derived from mouse embryonic stem cells improves motor function of hemiplegic mice. Cell Transplant, 2003, 12(5): 457–468

    Google Scholar 

  17. Chiba S, Ikeda R, Kurokawa M S, et al. Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage. J Neurol Sci, 2004, 219(1–2): 107–117

    Article  Google Scholar 

  18. Ye J, Yao K, Kim J C. Mesenchymal stem cell transplantation in a rabbit comeal alkali burn model: Engraftment and involvement in wound healing. Eye, 2006, 20(4): 482–490

    Article  Google Scholar 

  19. Guo T, Wang W, Zhang J, et al. Experimental study on repairing damage of corneal surface by mesenchymal stem cells transplantation. Chin J Ophthalmol (in Chinese), 2006, 42(3): 246–250

    Google Scholar 

  20. Ma Y, Xe Y, Xiao Z, et al. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stern Cells, 2006, 24(2): 315–321

    Article  Google Scholar 

  21. Izadpanah R, Joswig T, Tsien F, et al. Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesus macaques. Stem Cells Dev, 2005, 14(4): 440–451

    Article  Google Scholar 

  22. Pittenger M F, Mackay A M, Beck S C, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284: 143–147

    Article  Google Scholar 

  23. Horan P K, Melnicoff M J, Jensen B D, et al. Fluorescent cell labeling for in vivo and in vitro cell tracking. Methods Cell Biol, 1990, 33: 469–490

    Google Scholar 

  24. Fukuhara S, Tomita S, Nakatani T, et al. Comparison of cell labeling procedures for bone marrow cell transplantation to treat heart failure: Long-term quantitative analysis. Transplant Proc, 2002, 34: 2718–2721

    Article  Google Scholar 

  25. Liu J, Song G, Wang Z. Establishment of a corneal epithelial cell line spontaneously derived from human limbal cells. Exp Eye Res, 2007, 84(3): 599–609

    Article  Google Scholar 

  26. Rama P, Giannini R, Bruni A, et al. Further evaluation of amniotic membrane banking for transplantation in ocular surface diseases. Cell Tissue Bank, 2001, 2: 155–163

    Article  Google Scholar 

  27. Kruse F E, Joussen A M, Rohrschneider K, et al. Cryopreserved human amniotic membrane for ocular surface reconstruction. Graefes Arch Clin Exp Ophthalmol, 2000, 238: 68–75

    Article  Google Scholar 

  28. Friedenstein A J, Gorskaja U, Kalugina N N. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol, 1976, 4: 267–274

    Google Scholar 

  29. Woodbury D, Schwarz E J, Prockop D J, et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res, 2000, 61(4): 364–370

    Article  Google Scholar 

  30. Liechty K W, MacKenzie T C, Shaaban A F, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med, 2000, 6(11): 1282–1286

    Article  Google Scholar 

  31. Krause D S. Engraftment of bone marrow-derived epithelial cells. Ann N Y Acad Sci, 2005, 1044: 117–124

    Article  Google Scholar 

  32. Tremain N, Korkko J, Ibberson D, et al. MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages. Stem Cells, 2001, 19(5): 408–418

    Article  Google Scholar 

  33. Modesti A, Scarpa S, D’Orazi G, et al. Localization of type IV and V collagens in the stroma of human amnion. Prog Clin Biol Res, 1989, 296: 459–463

    Google Scholar 

  34. Fukuda K, Chikama T, Nakamura M, et al. Differential distribution of subchains of the basement membrane components type IV collagen and laminin among the amniotic membrane, cornea and conjunctiva. Cornea, 1999, 18: 73–79

    Article  Google Scholar 

  35. DiRenzo J, Signoretti S, Nakamura N, et al. Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res, 2002, 62(1): 89–98

    Google Scholar 

  36. Vicario-Abejon C, Yusta-Boyo M J, Fernandez-Moreno C, et al. Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia. J Neurosci, 2003, 23(3): 895–906

    Google Scholar 

  37. Harris R C. Potential physiologic roles for epidermal growth factor in the kidney. Am J Kidney Dis, 1991, 17(6): 627–630

    Google Scholar 

  38. Wolfgang C L, Lin C, Meng Q, et al. Epidermal growth factor activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases. J Gastrointest Surg, 2003, 7(1): 149–156

    Article  Google Scholar 

  39. Rubin A L, Rice R H. Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal human keratinocytes. Cancer Res, 1986, 46(5): 2356–2361

    Google Scholar 

  40. Chang J, Zhang C, Tani-Ishii N, et al. NF-kappaB activation in human dental pulp stem cells by TNF and LPS. J Dent Res, 2005, 84(11): 994–998

    Article  Google Scholar 

  41. Abdallah B M, Boissy P, Tan Q, et al. DLK1/FA1 regulates the function of human bone marrow mesenchymal stem cells (HMSC) by modulating gene expression of pro-inflammatory cytokines and immune-response-related factors. J Biol Chem, 2007, 282(10): 7339–7351

    Article  Google Scholar 

  42. Matic M, Petrov I N, Chen S, et al. Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity. Differentiation, 1997, 61(4): 251–260

    Article  Google Scholar 

  43. Pellegrini G, Dellambra E, Golisano O, et al. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci USA, 2001, 98(6): 3156–3161

    Article  Google Scholar 

  44. Sivak J M, Mohan R, Rinehart W B, et al. Pax-6 expression and activity are induced in the reepithelializing cornea and control activity of the transcriptional promoter for matrix metalloproteinase gelatinase B. Dev Biol, 2000, 222: 41–54

    Article  Google Scholar 

  45. Wolosin J M, Budak M T, Akinci M A. Ocular surface epithelial and stem cell development. Int J Dev Biol, 2004, 48(8–9): 981–991

    Article  Google Scholar 

  46. Heckmann L, Fiedler J, Mattes T, et al. Mesenchymal progenitor cells communicate via alpha and beta integrins with a three-dimensional collagen type I matrix. Cells Tissues Organs, 2006, 182(3–4): 143–154

    Article  Google Scholar 

  47. Nakagawa H, Akita S, Fukui M, et al. Human mesenchymal stem cells successfully improve skin-substitute wound healing. Br J Dermatol, 2005, 153(1): 29–36

    Article  Google Scholar 

  48. Wagers A J, Sherwood R I, Christensen J L, et al. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science, 2002, 297: 2256–2259

    Article  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Yuan Jing, Huang Bing, Liu BingQian, Liu JingBo, Jiang RuZhang & Ge Jian

  2. Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangzhou, 510080, China

    Yuan Jing, Jiang RuZhang & Ge Jian

  3. Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Yu JianXiong

Authors
  1. Yuan Jing
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  2. Yu JianXiong
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  3. Huang Bing
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  4. Liu BingQian
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  5. Liu JingBo
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  6. Jiang RuZhang
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  7. Ge Jian
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Corresponding author

Correspondence to Ge Jian.

Additional information

Supported by the Key Clinical Program of the Ministry of Health of China (Grant No. 2004468), the National Natural Science Foundation of China (Grant No. 30672275), Natural Science Foundation of Guangdong Province (Grant No. 06300679) and the Post-doctor Foundation of China (Grant No. 2005037616)

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Yuan, J., Yu, J., Huang, B. et al. Induction of corneal epithelial progenitors from bone-marrow mesenchymal stem cells of rhesus monkeys in vitro . CHINESE SCI BULL 52, 2216–2225 (2007). https://doi.org/10.1007/s11434-007-0304-z

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  • DOI: https://doi.org/10.1007/s11434-007-0304-z

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