Human adipose tissue-derived stromal cell therapy prevents bone loss in ovariectomized nude mouse.
Osteoporosis is a skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of cell therapy of human adipose tissue-derived stromal cell (ADSC) on ovariectomy-induced bone loss in T cell deficient nude mice. Twelve-week-old female nude mice underwent ovariectomy and were treated with ADSC, estrogen, or phosphate buffered saline (PBS). Whole body BMD revealed that treatment of ADSC was more protective against ovariectomy-induced attenuation in bone mass gain compared with PBS control after cell therapy (8.4±1.1 vs. 2.4%±1.4%, p<0.05 at 4 weeks, 13.7±1.3 vs. 7.7%±1.8%, p<0.05 at 8 weeks) and this effect was comparable to that of estrogen. μCT analysis revealed that the effect of ADSCs was specific to trabecular bone. Serum osteocalcin levels were increased 4 weeks after ovariectomy and treatment with ADSCs (76.4±11.6 ng/mL) increased osteocalcin to a greater extent when compared with estrogen (63.1±6.7 ng/mL, p<0.05) or PBS treatment (58.0±9.2 ng/mL, p<0.05). Flow cytometry analysis for PKH26-labeled ADSCs and quantitative real-time PCR analysis for human β-globin from bone revealed that transplanted ADSCs were trafficking in bone 48 h after injection and subsequently disappeared. There was no evidence of long-term engraftment of infused ADSCs in bone. In vitro, treatment with ADSC-conditioned medium enhanced osteogenic differentiation in stromal cells and preosteoblasts. These results suggest that cell therapy of ADSCs protects against ovariectomy-induced bone loss in nude mice in a paracrine manner.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Sun Wook
SW
Cho
Hyun Jin
HJ
Sun
Jae-Yeon
JY
Yang
Joo Yeon
JY
Jung
Hyung Jin
HJ
Choi
Jee Hyun
JH
An
Sang Wan
SW
Kim
Seong Yeon
SY
Kim
Kyu-Joo
KJ
Park
Chan Soo
CS
Shin
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects*; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology