Heng Zhu

Nonpharmaceutical interventions (NPIs) are important public health tools to fight against COVID-19. Governments around the world have instituted a variety of NPIs to modify individuals’ behavior, giving rise to four distinct pandemic response strategies: nudge, mandate, decree, and boost. To better understand the different policy choices involved in these strategies, four countries including Sweden, China, France, and Japan were compared to identify the critical institutional and cultural determinants of national response strategy. The finding shows that various responses regarding same threat are dependent on the distinctive institutional arrangements and cultural orientation of each country, and thus, there is no One-Size-Fits-All strategy.

Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have been used in clinical trials to treat acute graft-versus-host disease (aGvHD), although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD model, MSCs delayed the development of the disease. Interestingly, we found that MSC infusion increased the number of T lymphocytes in the secondary lymphoid organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for lymphocyte migration into SLOs, the in vitro experiments revealed that in the presence of MSCs, T lymphocytes (including CD4(+)CD25(+) regulatory T cells) preferred to take the naive-like phenotype (CD62L(+)/CCR7(+)) in mixed lymphocyte reaction and maintained the migratory activity elicited by secondary lymphoid tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune response. CCR7 expression is pivotal for their maturation and migration into SLOs. However, CCR7 expression and SLC-driven migratory activity of DCs were remarkably suppressed by MSC coculture. The processes above were realized mainly through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes to take CD62L(+)/CCR7(+) phenotype and decreased the CCR7 expression and proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory properties of T cells and DCs might contribute to the immunosuppressive activity of transplanted MSCs in the setting of aGvHD. Disclosure of potential conflicts of interest is found at the end of this article.

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal-distal and anterior-posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Background: Platelet-rich plasma (PRP) has been considered a promising tool for cartilage regeneration. However, increasing evidence has demonstrated the controversial effects of PRP on tissue regeneration, partially due to the unsatisfactory cell source. Chondrogenic progenitor cells (CPCs) have gained increasing attention as a potential cell source due to their self-renewal and multipotency, especially toward the chondrogenic lineage, and, thus, may be an appropriate alternative for cartilage engineering. Purpose: To compare the effects of PRP on CPC, mesenchymal stem cell (MSC), and chondrocyte proliferation, chondrogenesis, and cartilage regeneration. Study Design: Controlled laboratory study. Methods: Whole blood samples were obtained from 5 human donors to create PRPs (0, 1000 × 10 9 , and 2000 × 10 9 platelets per liter). The proliferation and chondrogenesis of CPCs, bone marrow–derived MSCs (BMSCs), and chondrocytes were evaluated via growth kinetic and CCK-8 assays. Immunofluorescence, cytochemical staining, and gene expression analyses were performed to assess chondrogenic differentiation and cartilaginous matrix formation. The in vivo effects of CPCs, BMSCs, and chondrocytes on cartilage regeneration after PRP treatment were measured by use of histopathological, biochemical, and biomechanical techniques in a cartilage defect model involving mature male New Zealand White rabbits (critical size, 5 mm). Results: The CPCs possessed migration abilities and proliferative capacities superior to those of the chondrocytes, while exhibiting a chondrogenic predisposition stronger than that of the BMSCs. The growth kinetic, CCK-8, cytochemical staining, and biochemical analyses revealed that the CPCs simultaneously displayed a higher cell density than the chondrocytes and stronger chondrogenesis than the BMSCs after PRP stimulation. In addition, the in vivo study demonstrated that the PRP+CPC construct yielded better histological (International Cartilage Repair Society [ICRS] score, mean ± SEM, 1197.2 ± 163.2) and biomechanical (tensile modulus, 1.523 ± 0.194) results than the PRP+BMSC (701.1 ± 104.9, P < .05; 0.791 ± 0.151, P < .05) and PRP+chondrocyte (541.6 ± 98.3, P < .01; 0.587 ± 0.142, P < .01) constructs at 12 weeks after implantation. Conclusion: CPCs exhibit superiority over MSCs and chondrocytes in PRP scaffold-based cartilage regeneration, and PRP+CPC treatment may be a favorable strategy for cartilage repair. Clinical Relevance: These findings provide evidence highlighting the preferable role of CPCs as a cell source in PRP-mediated cartilage regeneration and may help researchers address the problem of unsatisfactory cell sources in cartilage engineering.