Human second-trimester fetal liver-derived mesenchymal stromal cells are more effective than adult bone marrow MSCs for their superior growth kinetics, immunomodulatory, and osteogenic potential.

BACKGROUND: Mesenchymal stromal cells (MSCs) are promising candidates for cell therapy. Most of the therapeutic applications have used adult bone marrow MSCs, adipose MSCs and perinatal tissue-derived MSCs. Recent evidence suggests that MSCs from mid-gestational fetal tissues are more primitive, grow faster and are biologically more closely related to embryonic stem cells than other sources of MSCs. However, the expression of pluripotency genes raises the question of whether these genes are safe for clinical application. In this study, we demonstrated that second-trimester fetal liver-derived MSCs lack the expression of pluripotent markers and maintain their proliferative and osteogenic differentiation potential beyond passage 12. Compared to other sources, FL-MSCs exhibit characteristics that are promising for use in skeletal regeneration.

METHODS: MSCs were isolated from the second-trimester fetal liver and characterized for surface antigen expression, pluripotency marker expression and multilineage differentiation. The growth kinetics, population doubling, and number of colony-forming units were analyzed at the 3rd, 5th, 8th and 10th passages of FLMSCs and compared with those of BMMSCs. The immunomodulatory properties of FLMSCs were analyzed by a T-cell proliferation assay. The osteogenic differentiation potential of FL-MSCs was assessed at passages 3, 5, 8 and 12 and compared with that of BMMSCs.

RESULTS: We demonstrated that second-trimester fetal liver-derived MSCs exhibited a distinct fibroblast-like spindle-shaped morphology and expressed typical MSC surface antigens. Unlike first-trimester fetal MSCs, second-trimester FL-MSCs did not express pluripotent markers and showed significantly greater self-renewal and proliferative potential at higher passages and a lower apoptotic rate than BM-MSCs. Additionally, the osteogenic differentiation potential of FL-MSCs was 4-6 times greater than that of BM-MSCs at both early and late passages CONCLUSION: Our findings underscore the robust self-renewal and proliferative potential of second-trimester fetal liver-derived MSCs, which notably lack pluripotent markers. The ability of FL-MSCs to sustain osteogenic potential through multiple passages makes them promising candidates for bone tissue engineering and regenerative medicine.