Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoi

Summary:

The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC “niche” involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.

Benedetto Sacchetti,¹,³,⁸ Alessia Funari,³,⁴,⁸ Stefano Michienzi,¹,³ Silvia Di Cesare,³ Stefania Piersanti,³ Isabella Saggio,²,³,⁵ Enrico Tagliafico,⁶ Stefano Ferrari,⁶ Pamela Gehron Robey,⁷ Mara Riminucci,³,⁴ and Paolo Bianco¹,³,

¹ Deparment of Experimental Medicine, La Sapienza University, 00161 Rome, Italy
² Department of Genetics & Molecular Biology, La Sapienza University, 00161 Rome, Italy
³ Biomedical Science Park San Raffaele, 00128 Rome, Italy
⁴ Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy
⁵ Institute for Molecular Biology and Pathology, National Research Council, Rome, Italy
⁶ Department of Biochemistry, University of Modena, 59100 Modena, Italy
⁷ Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA

Corresponding author
Paolo Bianco
p.bianco@flashnet.it