The Use of Blood Vessel-Derived Stem Cells for Meniscal Regeneration and Repair

OSAWA, A., C. D. HARNER, B. GHARAIBEH, T. MATSUMOTO, Y. MIFUNE, S. KOPF, S. J. M. INGHAM, V. SCHREIBER, A. USAS, and J. HUARD. The Use of Blood Vessel-Derived Stem Cells for Meniscal Regeneration and Repair. Med. Sci. Sports Exerc., Vol. 45, No. 5, pp. 813-823, 2013. Purpose: Surgical repairs of tears in the vascular region of the meniscus usually heal better than repairs performed in the avascular region; thus, we hypothesized that this region might possess a richer supply of vascular-derived stem cells than the avascular region. Methods: In this study, we analyzed 6 menisci extracted from aborted human fetuses and 12 human lateral menisci extracted from adult human subjects undergoing total knee arthroplasty. Menisci were immunostained for CD34 (a stem cell marker) and CD146 (a pericyte marker) in situ, whereas other menisci were dissected into two regions (peripheral and inner) and used to isolate meniscus-derived cells by flow cytometry. Cell populations expressing CD34 and CD146 were tested for their multi-lineage differentiation potentials, including chondrogenic, osteogenic, and adipogenic lineages. Fetal peripheral meniscus cells were transplanted by intracapsular injection into the knee joints of an athymic rat meniscal tear model. Rat menisci were extracted and histologically evaluated after 4 wk posttransplantation. Results: Immunohistochemistry and flow cytometric analyses demonstrated that a higher number of CD34-and CD146-positive cells were found in the peripheral region compared with the inner region. The CD34-and CD146-positive cells isolated from the vascular region of both fetal and adult menisci demonstrated multilineage differentiation capacities and were more potent than cells isolated from the inner (avascular) region. Fetal CD34-and CD146-positive cells transplanted into the athymic rat knee joint were recruited into the meniscal tear sites and contributed to meniscus repair. Conclusions: The vascularized region of the meniscus contains more stem cells than the avascular region. These meniscal-derived stem cells were multi-potent and contributed to meniscal regeneration.