Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

The loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain. Here, we demonstrate that the implantation of human iPS cell-derived cartilaginous tissue (hiPS-Cart) restores this loss by replacing lost NP spatially and functionally. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. Single cell RNA sequencing (scRNA-seq) analysis revealed that cells in hiPS-Cart corresponded to chondrocyte-like NP cells but not to notochordal NP cells. The implantation of hiPS-Cart into a nuclectomized space of IVD in nude rats prevented the degeneration of the IVD and preserved its mechanical properties. hiPS-Cart survived and occupied the nuclectomized space for at least six months after implantation, indicating spatial and functional replacement of lost NP by hiPS-Cart. Further scRNA-seq analysis revealed that hiPS-Cart cells changed their profile after implantation, differentiating into two lineages that are metabolically distinct from each other. However, post-implanted hiPS-Cart cells corresponded to chondrocyte-like NP cells only and did not develop into notochordal NP cells, suggesting that chondrocyte-like NP cells are nearly sufficient for NP function. The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.Kamatani T., Hagizawa H., Yarimitsu S., et al. Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus. Biomaterials 284, 121491 (2022); https://doi.org/10.1016/j.biomaterials.2022.121491

Effects of Initial Graft Tension during Anterior Talofibular Ligament Reconstruction on Ankle Kinematics, Laxity, and In-situ Forces of the Reconstructed Graft

前距腓靭帯は，足関節の安定性に関わる重要な靱帯である．前距腓靱帯の損傷後に慢性的な足関節の不安定性が残存した場合，前距腓靱帯再建手術が必要となるが，その際に再建靭帯にかける適切な張力について研究した報告はなかった．本論文では，再建靭帯にかける張力の違いが，足関節のキネマティクス，制動性，術後の靱帯張力に及ぼす影響と適切な再建靭帯初期固定張力を明らかにした

Effect of collagen-induced residual stress on the frictional property of articular cartilage

Previous findings, such as split-line of the articular cartilage surface and curving of sliced cartilage specimen, would suggest that residual stress is contained in articular cartilage. This study was performed to determine the effect of collagen fibre-induced residual stress on the biphasic lubrication property of articular cartilage. A fibre-reinforced poroelastic model of articular cartilage was developed in Abaqus. In the model, residual stress was contained in the collagen fibre in the surface layer by applying 1–5% of tensile strain. Reciprocating friction analysis was performed between the model and a sphere at a friction speed of 1.0–10.0 mm/s. Results revealed that the coefficients of start-up and dynamic friction at second friction cycle were lower in residual stress model than in no-residual stress model, with the largest decreases observed at a friction speed of 1 mm/s. It was observed that rehydration was promoted in the bearing area in residual stress model. These results suggest that collagen-induced residual stress plays an important role in enhancing the biphasic lubrication property of articular cartilage

Guideline for design of substrate stiffness for mesenchymal stem cell culture based on heterogeneity of YAP and RUNX2 responses

Mesenchymal stem cells (MSCs) have the potential for self-renewal and multipotency to differentiate into various lineages. Thus, they are of great interest in regenerative medicine as a cell source for tissue engineering. Substrate stiffness is one of the most extensively studied exogenous physical factors; however, consistent results have not always been reported for controlling MSCs. Conventionally used stiff culture substrates, such as tissue-culture polystyrene and glass, enhance nuclear localization of a mechanotransducer YAP and a pre-osteogenic transcription factor RUNX2, and bias MSCs towards the osteogenic lineage, even without osteogenic-inducing soluble factors. The mechanosensitive nature and intrinsic heterogeneity present challenges for obtaining reproducible results. This review summarizes the heterogeneity in human MSC response, specifically, nuclear/cytoplasmic localization changes in the mechanotransducer yes-associated protein (YAP) and the osteogenic transcription factor RUNX2, in response to substrate stiffness. In addition, a perspective on the intracellular factors attributed to response heterogeneity is discussed. The optimal range of stiffness parameters, Young’s modulus, for MSC expansion culture to suppress osteogenic differentiation bias through the suppression of YAP and RUNX2 nuclear localization, and cell cycle progression is likely to be surprisingly narrow for a cell population from an identical donor and vary among cell populations from different donors. We believe that characterization of the heterogeneity of MSCs and understanding their biological meaning is an exciting research direction to establish guidelines for the design of culture substrates for the sophisticated control of MSC properties