Expression of CD105 and CD34 receptors controls BMP-induced in vitro mineralization of mouse adipose-derived stem cells but does not predict their in vivo bone-forming potential.
Adipose-derived stem cells (ADSCs) can be excellent alternative to bone marrow derived stem cells for enhancing fracture repair since ADSCs can be isolated comparatively in large numbers from discarded lipoaspirates. However, osteogenic potential of ADSCs in vivo is very controversial. We hypothesized that adipose-derived stem cells (ADSCs) that respond maximally to bone morphogenetic proteins (BMPs) in vitro would possess maximum bone-forming potential. Four purified populations of mouse ADSCs: CD105(+) CD34(+), CD105(-) CD34(-), CD105(+) CD34(-) and CD105(-) CD34(+) were obtained using fluorescence-activated cell sorting (FACS) and their BMP-responsiveness was determined in vitro. CD105(+) CD34(-) population showed the strongest response to BMPs in terms of robust increase in mineralization. Expression of CD105 correlated with high BMP-responsive phenotype and larger cell size while expression of CD34 correlated with low BMP-responsive phenotype and smaller cell size. CD105(+) CD34(-) population displayed higher gene expression of Alk1 or Alk6 receptors in comparison with other populations. However, CD105(+) CD34(-) ADSCs failed to induce ectopic bone formation in vivo after they were transplanted into syngeneic mice, indicating that in vitro BMP-responsiveness is not a good indicator to predict in vivo bone forming potential of ADSCs. Therefore greater precautions should be executed during selection of competent ADSCs for bone repair.
Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, School of Medicine, University of Virginia, Charlottesville, Virginia, 22908.
Vedavathi
V
Madhu
Allison
A
Kilanski
Nikitha
N
Reghu
Abhijit S
AS
Dighe
Quanjun
Q
Cui
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins; D002113:Calcification, Physiologic; D000071063:Endoglin; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells / Q000502:physiology*
D018952:Antigens, CD34; D019485:Bone Morphogenetic Proteins; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins
ADSCs; BMPs; CD105+CD34−; bone formation; cell size