Chondrogenic and BMP-4 primings confer osteogenesis potential to human cord blood mesenchymal stromal cells delivered with biphasic calcium phosphate ceramics

Abstract

Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.

Biomimetic versus sintered macroporous calcium phosphate scaffolds enhanced bone regeneration and human mesenchymal stromal cell engraftment in calvarial defects

“…Cell therapies can be combined with CaPs to enhance their osteogenic potential [16][17][18]. Biomaterial constructs act as delivery vehicles, provide regenerative cues, and act as structural scaffolds to permit the influx of host cells and regeneration of tissue.…”

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

“…Kern et al reported that CB-MSCs could not differentiate toward adipocytes, similar findings were also reported for PL-MSCs (238). Other investigators, besides confirming the low adipogenic potential of CB-MSC (258), have reported higher osteogenic (247,259) and chondrogenic potential (257,260). Differences in identical genetic background perinatal MSC sources have also been described, with strikingly inconsistent results reported from AM-MSCs (216).…”

First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome

“…They can be isolated from several adult and fetal tissues, including bone marrow and umbilical cord blood (CB) [8,9]. MSCs are well-known to contribute to tissue repair in chondrogenic and osteogenic damaged tissues [10] and reduce apoptosis in damaged cells supporting tissue regeneration [11][12][13], but the most clinically relevant therapeutic effect relies on their immunomodulatory properties. Indeed, MSCs interact with each cellular component of the immune system.…”