再生医学ジャーナル

Identification and Expansion of Adipose Stem Cells with Enhanced Bone Regeneration Properties

Di Stefano AB, Leto Barone AA, Giammona A, Apuzzo T, Moschella P, Di Franco S, Giunta G, Carmisciano M, Eleuteri C, Todaro M, Dieli F, Cordova A, Stassi G and Moschella F

Introduction: Adipose tissue represents an abundant source of mesenchymal stem-like cells. Adipose-derived stem cell progeny have been investigated and used in regenerative medicine for decades. In the last few years, they have been used to “enrich” lipoaspirates in fat grafting techniques, in an attempt to boost the regenerative potential of adipose tissue when used as autologous “filler”.

Materials and Methods: 50 adipose tissue samples from lipoaspirates and subcutaneous breast tissue biopsies were used to generate adipose floating spheroid cell (ASphC) lines. ASphC were characterized for the expression of putative mesenchymal stem cell markers and used in vitro to test their multilineage potential. Furthermore, ASphCs were seeded on dermal regeneration template (Integra®) and implanted into the T8 vertebral laminectomy site of immunocompromised mice.

Results: Here, we show that the majority of ASphCs are in a quiescent state and express the putative surface stem cell marker CD271. Unlike CD271- cells, CD271+ ASphCs grew indefinitely in vitro as undifferentiated spheres in serum-free medium, maintaining their multilineage differentiation potential ability. Importantly, p107, a functional adipose stem cell marker, is strictly expressed in ASphCs and barely present in their differentiated mesenchymal lineages. These sphere cells display an enhanced ability in vitro to differentiate into distinctive end-stage cell types, such as osteoblasts, chondrocytes and adipocytes. Gene expression profiling analysis indicated that ASphCs are endowed with stem cell potential that is gradually lost during specific differentiation. Finally, ASphCs facilitate bone inter body repair and regeneration after laminectomy.

Conclusions: We conclude that ASphCs possess a pronounced in vivo activity to regenerate the bone injury. Overall, ASphCs represent a heterogeneous population of stem-like cells harbouring multilineage differential potential and representing a prospective promising tool in cell therapy and tissue engineering.