Fetal subcutaneous cells have potential for autologous tissue engineering

Abstract

Major congenital malformations affect up to 3% of newborns. Infants with prenatally diagnosed soft tissue defects should benefit from having autologous tissue readily available for surgical implantation in the perinatal period. In this study, we investigate fetal subcutaneous cells as cellular source for tissue engineering. Fetal subcutaneous biopsies were collected from elective terminations at gestational Week 20-21. Cells were isolated, expanded, and characterized in vitro. To determine cell coverage, localization, viability, and proliferation in different constructs, the cells were seeded onto a matrix (small intestine submucosa) or in collagen gel with or without poly(ε-caprolactone) mesh and were kept in culture for up to 8 weeks before analysis. Angiogenesis was analysed through a tube-forming assay. Fetal subcutaneous cells could be expanded until 43 ± 3 population doublings, expressed mesenchymal markers, and readily differentiate into adipogenic and osteogenic lineages. The cells showed low adherence to small intestine submucosa and did not migrate deep into the matrix. However, in collagen gels, the cells migrated into the gel and proliferated with sustained viability for up to 8 weeks. The cells in the matrices expressed Ki67, CD73, and α-smooth muscle actin but not cytokeratin or CD31. Fetal cells derived from subcutaneous tissue demonstrated favourable characteristics for preparation of autologous tissue transplants before birth. Our study supports the theory that cells could be obtained from the fetus during pregnancy for tissue engineering purposes after birth. In a future clinical situation, autologous transplants could be used for reconstructive surgery in severe congenital malformations.

Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies

“…The skin is the body's largest organ and skin‐residing stem cells are rather accessible. MSC has been successfully isolated from both pre‐ and postnatal human dermis and subcutaneous tissue . Fetal subcutaneous MSC‐like cells show high proliferative capacity which is favorable for the cell yield, but still within the Hayflick limit indicating stable, non‐embryonic cell phenotypes .…”

“…MSC has been successfully isolated from both pre‐ and postnatal human dermis and subcutaneous tissue . Fetal subcutaneous MSC‐like cells show high proliferative capacity which is favorable for the cell yield, but still within the Hayflick limit indicating stable, non‐embryonic cell phenotypes . Adult dermal MSC promotes wound healing and modulates immune responses in mice, which show that these cells have similar characteristics as adult BM‐MSC.…”