title: Age-associated reduction of the count and functional activity of stromal precursor cells can be caused by both true reduction (exhaustion) of cell pool and regulatory effects of the organism.
abstract: The study was carried out on CBA mice using the method of heterotopic transplantation. A fragment of the femoral bone marrow (1/2) or spleen (1/5 of the organ) was transplanted under the renal capsule of a recipient. The following donor-recipient cross-transplantation variants were studied: young-young (Y-Y), young-old (Y-O), old-old (O-O), and old-young (O-Y). Cell suspensions were prepared from 2-month transplants inoculated in monolayer cultures and the cloning efficiency (ECF-F) of stromal precursor cells (CFC-F) was evaluated. The bone marrow transplant ECF-F and the count of CFC-F in the O-O group were 8-fold lower than in the Y-Y group. In the O-Y group, ECF-F was 3-fold higher than in the O-O group, but by 2.5 times lower than in the Y-Y group. ECF-F in Y-O group was 2-fold lower than in Y-Y group. The ECF-F and CFC-F count in spleen transplants in the O-O group were 4- and 6-fold lower, respectively, than in Y-Y group. However, in O-Y group ECF-F was 7-fold higher than in O-O group and higher than even in Y-Y group. The weight of induced ectopic bone tissue after transplantation of the osteoinductor (fragments of the allogenic urinary bladder mucosa) was 2-fold lower in the O-O vs. Y-Y group. However, comparison of the ectopic bone tissue weights in different experimental groups showed that osteoinductor activity of the bladder epithelium did not decrease, but increased 3-fold with age (O-Y:Y-Y). A 5-fold reduction of this proportion in groups where the osteoinductor was transplanted from old donors to old and young recipients (O-Y:O-O) could be attributed to age-specific reduction of the count of inducible osteogenic precursor cells (IOPC). The data in general suggest that age-specific reduction of the stromal precursor count and functional activity could be caused by the true reduction (exhaustion) of cell pool (bone marrow CFC-F; presumably, IOPC) and by the regulatory effects of the organism (bone marrow and splenic CFC-F, IOPC). These data seem to be significant for understanding of the role of osteogenic stromal precursor cells in the development of age-associated bone tissue defects, for example, senile osteoporosis.
authors.affiliation: Laboratory of Immunity Regulation, N. F. Gamaleya Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Russia. uliya.gorskaya@nearmedic.ru
authors.forename: Yu F
authors.initials: YF
authors.lastname: Gorskaya
authors.forename: T A
authors.initials: TA
authors.lastname: Danilova
authors.forename: V G
authors.initials: VG
authors.lastname: Nesterenko
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018920:Coculture Techniques; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010012:Osteogenesis; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology*; D016042:Transplantation, Heterotopic; D001743:Urinary Bladder / Q000166:cytology / Q000637:transplantation