Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects

Wenchuan Chen, Jun Liu, Navid Manuchehrabadi, Michael D. Weir, Zhimin Zhu, Hockin H.K. Xu

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be harvested at a low cost without an invasive procedure. However, there has been no report on comparing hUCMSCs with human bone marrow MSCs (hBMSCs) for bone regeneration invivo. The aim of this study was to investigate hUCMSC and hBMSC seeding on macroporous calcium phosphate cement (CPC), and to compare their bone regeneration in critical-sized cranial defects in rats. Cell attachment, osteogenic differentiation and mineral synthesis on RGD-modified macroporous CPC were investigated invitro. Scaffolds with cells were implanted in 8-mm defects of athymic rats. Bone regeneration was investigated via micro-CT and histological analysis at 4, 12, and 24 weeks. Three groups were tested: CPC with hUCMSCs, CPC with hBMSCs, and CPC control without cells. Percentage of live cells and cell density on CPC invitro were similarly good for hUCMSCs and hBMSCs. Both cells had high osteogenic expressions of alkaline phosphatase, osteocalcin, collagen I, and Runx2. Bone mineral density and trabecular thickness in hUCMSC and hBMSC groups invivo were greater than those of CPC control group. New bone amount for hUCMSC-CPC and hBMSC-CPC constructs was increased by 57% and 88%, respectively, while blood vessel density was increased by 15% and 20%, than CPC control group at 24 weeks. hUCMSC-CPC and hBMSC-CPC groups generally had statistically similar bone mineral density, new bone amount and vessel density. In conclusion, hUCMSCs seeded on CPC were shown to match the bone regeneration efficacy of hBMSCs invivo for the first time. Both hUCMSC-CPC and hBMSC-CPC constructs generated much more new bone and blood vessels than CPC without cells. Macroporous RGD-grafted CPC with stem cell seeding is promising for craniofacial and orthopedic repairs.

Original languageEnglish (US)
Pages (from-to)9917-9925
Number of pages9
JournalBiomaterials
Volume34
Issue number38
DOIs
StatePublished - Dec 2013
Externally publishedYes

Bibliographical note

Funding Information:
We are indebted to Prof. David J. Mooney at Harvard University for fruitful discussions on animal studies. We thank Dr. Chen Chen of University of Maryland School of Dentistry for assisting animal surgery, Dr. Cindy Zhou of University of Maryland School of Dentistry for help with histological images, and Prof. Liang Zhu of Mechanical Engineering Department at University of Maryland Baltimore County for help with micro-CT. This study was supported by NIH R01 DE14190 and R21 DE22625 (HX), National Natural Science Foundation of China 81000455 (WC), and University of Maryland School of Dentistry .

Keywords

  • Athymic rats
  • Bone regeneration
  • Calcium phosphate cement
  • Critical-sized cranial defect
  • RGD
  • Stem cells

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