Human umbilical cord blood-derived CD34+ cells reverse osteoporosis in NOD/SCID mice by altering osteoblastic and osteoclastic activities

Reeva Aggarwal, Jingwei Lu, Suman Kanji, Matthew Joseph, Manjusri Das, Garrett J. Noble, Brooke K. McMichael, Sudha Agarwal, Richard T. Hart, Zongyang Sun, Beth S. Lee, Thomas J. Rosol, Rebecca Jackson, Hai Quan Mao, Vincent J. Pompili, Hiranmoy Das

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: Osteoporosis is a bone disorder associated with loss of bone mineral density and micro architecture. A balance of osteoblasts and osteoclasts activities maintains bone homeostasis. Increased bone loss due to increased osteoclast and decreased osteoblast activities is considered as an underlying cause of osteoporosis. Methods and Findings: The cures for osteoporosis are limited, consequently the potential of CD34+ cell therapies is currently being considered. We developed a nanofiber-based expansion technology to obtain adequate numbers of CD34+ cells isolated from human umbilical cord blood, for therapeutic applications. Herein, we show that CD34+ cells could be differentiated into osteoblastic lineage, in vitro. Systemically delivered CD34+ cells home to the bone marrow and significantly improve bone deposition, bone mineral density and bone micro-architecture in osteoporotic mice. The elevated levels of osteocalcin, IL-10, GM-CSF, and decreased levels of MCP-1 in serum parallel the improvements in bone micro-architecture. Furthermore, CD34+ cells improved osteoblast activity and concurrently impaired osteoclast differentiation, maturation and functionality. Conclusions: These findings demonstrate a novel approach utilizing nanofiber-expanded CD34+ cells as a therapeutic application for the treatment of osteoporosis.

Original languageEnglish (US)
Article numbere39365
JournalPloS one
Volume7
Issue number6
DOIs
StatePublished - Jun 18 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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