Open AccessReversing bone loss by directing mesenchymal stem cells to bone
Author(s) -
Yao Wei,
Guan Min,
Jia Junjing,
Dai Weiwei,
Lay YuAn E.,
Amugongo Sarah,
Liu Ruiwu,
Olivos David,
Saunders Mary,
Lam Kit S.,
Nolta Jan,
Olvera Diana,
Ritchie Robert O.,
Lane Nancy E.
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1461
Subject(s) - mesenchymal stem cell , homing (biology) , biology , osteoblast , cancer research , microbiology and biotechnology , transplantation , stem cell , endocrinology , medicine , in vitro , biochemistry , ecology
Bone regeneration by systemic transplantation of mesenchymal stem cells (MSCs) is problematic due to the inability to control the MSCs' commitment, growth, and differentiation into functional osteoblasts on the bone surface. Our research group has developed a method to direct the MSCs to the bone surface by conjugating a synthetic peptidomimetic ligand (LLP2A) that has high affinity for activated α4β1 integrin on the MSC surface, with a bisphosphonates (alendronate) that has high affinity for bone (LLP2A‐Ale), to direct the transplanted MSCs to bone. Our in vitro experiments demonstrated that mobilization of LLP2A‐Ale to hydroxyapatite accelerated MSC migration that was associated with an increase in the phosphorylation of Akt kinase and osteoblastogenesis. LLP2A‐Ale increased the homing of the transplanted MSCs to bone as well as the osteoblast surface, significantly increased the rate of bone formation and restored both trabecular and cortical bone loss induced by estrogen deficiency or advanced age in mice. These results support LLP2A‐Ale as a novel therapeutic option to direct the transplanted MSCs to bone for the treatment of established bone loss related to hormone deficiency and aging. S tem C ells 2013;31:2003‐2014