Sage Journals: Discover world-class research

Abstract

The aim of this study was to determine if endothelial cells could enhance bone marrow stromal-cell-mediated bone regeneration in an osseous defect. Using poly-lactide-co-glycolide scaffolds as cell carriers, we transplanted bone marrow stromal cells alone or with endothelial cells into 8.5-mm calvarial defects created in nude rats. Histological analyses of blood vessel and bone formation were performed, and microcomputed tomography (μCT) was used to assess mineralized bone matrix. Though the magnitude of the angiogenic response between groups was the same, μCT analysis revealed earlier mineralization of bone in the co-transplantation condition. Ultimately, there was a significant increase (40%) in bone formation in the co-transplantation group (33 ± 2%), compared with the transplantation of bone marrow stromal cells alone (23 ± 3%). Analysis of these data demonstrates that, in an orthotopic site, transplanted endothelial cells can influence the bone-regenerative capacity of bone marrow stromal cells.

Get full access to this article

View all access options for this article.

References

Akita S, Fukui M, Nakagawa H, Fujii T, Akino K (2004). Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor. Wound Repair Regen 12:252–259.

Bidic SM, Calvert JW, Marra K, Kumta P, Campbell P, Mitchell R, et al. (2003). Rabbit calvarial wound healing by means of seeded Caprotite scaffolds. J Dent Res 82:131–135.

Blum JS, Barry MA, Mikos AG, Jansen JA (2003). In vivo evaluation of gene therapy vectors in ex vivo-derived marrow stromal cells for bone regeneration in a rat critical-size calvarial defect model. Hum Gene Ther 14:1689–1701.

Bouletreau PJ, Warren SM, Spector JA, Peled ZM, Gerrets RP, Greenwald JA, et al. (2002). Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Plast Reconstr Surg 109:2384–2397.

Bruder SP, Kurth AA, Shea M, Hayes WC, Jaiswal N, Kadiyala S (1998). Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res 16:155–162.

Collin-Osdoby P (1994). Role of vascular endothelial cells in bone biology. J Cell Biochem 55:304–309.

Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK, Gorskaya UF, Kuralesova AI, Latzinik NW, et al. (1978). Origin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants. Exp Hematol 6:440–444.

Fuchs S, Baffour R, Zhou YF, Shou M, Pierre A, Tio FO, et al. (2001). Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 37:1726–1732.

Gao J, Dennis JE, Solchaga LA, Awadallah AS, Goldberg VM, Caplan AI (2001). Tissue-engineered fabrication of an osteochondral composite graft using rat bone marrow-derived mesenchymal stem cells. Tissue Eng 7:363–371.

10.

Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999). VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628.

11.

Greenwald JA, Mehrara BJ, Spector JA, Warren SM, Crisera FE, Fagenholz PJ, et al. (2000). Regional differentiation of cranial suture-associated dura mater in vivo and in vitro: implications for suture fusion and patency. J Bone Miner Res 15:2413–2430.

12.

Ishaug-Riley SL, Crane GM, Gurlek A, Miller MJ, Yasko AW, Yaszemski MJ, et al. (1997). Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery. J Biomed Mater Res 36:1–8.

13.

Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, et al. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402.

14.

Kaigler D, Krebsbach PH, Polverini PJ, Mooney DJ (2003). Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells. Tissue Eng 9:95–103.

15.

Kaigler D, Krebsbach PH, West ER, Horger K, Huang YC, Mooney DJ (2005). Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J 19:665–667.

16.

Krebsbach PH, Kuznetsov SA, Satomura K, Emmons RV, Rowe DW, Robey PG (1997). Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. Transplantation 63:1059–1069.

17.

Krebsbach PH, Kuznetsov SA, Bianco P, Robey PG (1999). Bone marrow stromal cells: characterization and clinical application. Crit Rev Oral Biol Med 10:165–181.

18.

Latsinik NV, Gorskaia IF, Grosheva AG, Domogatskii SP, Kuznetsov SA (1986). [The stromal colony-forming cell (CFUf) count in the bone marrow of mice and the clonal nature of the fibroblast colonies they form]. Ontogenez 17:27–36 [article in Russian].

19.

Mehrara BJ, Most D, Chang J, Bresnick S, Turk A, Schendel SA, et al. (1999). Basic fibroblast growth factor and transforming growth factor beta-1 expression in the developing dura mater correlates with calvarial bone formation. Plast Reconstr Surg 104:435–444.

20.

Mooney DJ, Baldwin DF, Suh NP, Vacanti JP, Langer R (1996). Novel approach to fabricate porous sponges of poly(D,L-lactic-co-glycolic acid) without the use of organic solvents. Biomaterials 17:1417–1422.

21.

Nor JE, Peters MC, Christensen JB, Sutorik MM, Linn S, Khan MK, et al. (2001). Engineering and characterization of functional human microvessels in immunodeficient mice. Lab Invest 81:453–463.

22.

Ohgushi H, Okumura M, Tamai S, Shors EC, Caplan AI (1990). Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. J Biomed Mater Res 24:1563–1570.

23.

Peters MC, Polverini PJ, Mooney DJ (2002). Engineering vascular networks in porous polymer matrices. J Biomed Mater Res 60:668–678.

24.

Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM (2002). Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109:337–346.

25.

Schechner JS, Nath AK, Zheng L, Kluger MS, Hughes CC, Sierra-Honigmann MR, et al. (2000). In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proc Natl Acad Sci USA 97:9191–9196.

26.

Schmitz JP, Hollinger JO (1986). The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 205:299–308.

27.

Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, et al. (1998). Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367.

28.

Villanueva JE, Nimni ME (1990). Promotion of calvarial cell osteogenesis by endothelial cells. J Bone Miner Res 5:733–739.

29.

Villars F, Guillotin B, Amedee T, Dutoya S, Bordenave L, Bareille R, et al. (2002). Effect of HUVEC on human osteoprogenitor cell differentiation needs heterotypic gap junction communication. Am J Physiol Cell Physiol 282:C775–C785.

30.

Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG (1996). Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials 17:175–185.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.41 MB

Transplanted Endothelial Cells Enhance Orthotopic Bone Regeneration

Abstract

Get full access to this article

References

Supplementary Material