Single-Cell RNA-Sequencing Reveals the Skeletal Cellular Dynamics in Bone Repair and Osteoporosis.

The bone is an important organ that performs various functions, and the bone marrow inside the skeleton is composed of a complex intermix of hematopoietic, vascular, and skeletal cells. Current single-cell RNA sequencing (scRNA-seq) technology has revealed heterogeneity and sketchy differential hierarchy of skeletal cells. Skeletal stem and progenitor cells (SSPCs) are located upstream of the hierarchy and differentiate into chondrocytes, osteoblasts, osteocytes, and bone marrow adipocytes. In the bone marrow, multiple types of bone marrow stromal cells (BMSCs), which have the potential of SSPCs, are spatiotemporally located in distinct areas, and SSPCs' potential shift of BMSCs may occur with the advancement of age. These BMSCs contribute to bone regeneration and bone diseases, such as osteoporosis. In vivo lineage-tracing technologies show that various types of skeletal lineage cells concomitantly gather and contribute to bone regeneration. In contrast, these cells differentiate into adipocytes with aging, leading to senile osteoporosis. scRNA-seq analysis has revealed that alteration in the cell-type composition is a major cause of tissue aging. In this review, we discuss the cellular dynamics of skeletal cell populations in bone homeostasis, regeneration, and osteoporosis.

Characteristics and clinical potential of a cellularly modified gelatin sponge.

BACKGROUND: Human umbilical cord mesenchymal stem cells (HuMSCs) injected directly have been proven effective for improving chronic wounds. However, HuMSCs largely die within 14 days. The aim of study is to establish a cellularly modified gelatin sponge and investigate its characteristics and clinical potential. METHODS: HuMSCs were isolated, expanded and seeded in a poly-L-lysine (PLL)-coated gelatin sponge. Fabricated gelatin sponges were estimated through observation of morphological surface and ultrastructure, following confirmed by histology method. Supernatants were collected at different times for enzyme-linked immunosorbent assays (ELISAs) to measure growth factors. The cell embedded gelatin sponges were implanted subcutaneously on the backs of mice and the samples were harvested and studied histologically. RESULTS: HuMSCs gradually modified the gelatin sponge by depositing collagen and hyaluronic acid, and degrading the structure of gelatin, resulting in a dense, and elastic structure. Compared with cells cultured in monolayer, the levels of growth factors increased remarkably when HuMSCs were cultivated in the gelatin sponge. Upon subcutaneous implantation in the backs of mice, the cellularized gelatin sponges persisted for up to 2 months and eventually integrated into the host tissue, while blank gelatin sponges degraded completely by the end of the second month. CONCLUSION: Gelatin sponge is a clinically accessible scaffold for HuMSCs implantation to maintain short-term survival of the cells and high-level production of growth factors, which demonstrates good clinical potential for enhancing wound healing.