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


RESULTS
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.
Cardiovascular Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio, USA.
Reeva
R
Aggarwal
Jingwei
J
Lu
Suman
S
Kanji
Matthew
M
Joseph
Manjusri
M
Das
Garrett J
GJ
Noble
Brooke K
BK
McMichael
Sudha
S
Agarwal
Richard T
RT
Hart
Zongyang
Z
Sun
Beth S
BS
Lee
Thomas J
TJ
Rosol
Rebecca
R
Jackson
Hai-Quan
HQ
Mao
Vincent J
VJ
Pompili
Hiranmoy
H
Das
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001842:Bone and Bones / Q000648:ultrastructure; D002113:Calcification, Physiologic; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D010024:Osteoporosis / Q000378:metabolism / Q000628:therapy*
D018952:Antigens, CD34; D016207:Cytokines; D015675:Osteocalcin