“…We performed the RNA velocity analysis as described previously 50 . TAS-Seq data cDNA reads were mapped to the reference genome ( Macaca_fascicularis _6.0 for macaca fascicularis data, and GRCh38 release-101 for human data) using HISAT2-2.2.1 51 and the following parameters were used: -q -p 6 –rna-strandness F –very-sensitive –seed 656565 –reorder –omit-sec-seq –mm.…”
Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
“…We performed the RNA velocity analysis as described previously 50 . TAS-Seq data cDNA reads were mapped to the reference genome ( Macaca_fascicularis _6.0 for macaca fascicularis data, and GRCh38 release-101 for human data) using HISAT2-2.2.1 51 and the following parameters were used: -q -p 6 –rna-strandness F –very-sensitive –seed 656565 –reorder –omit-sec-seq –mm.…”
Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
“…The interaction mechanism of IDD is complicated and caused by many factors [ 11 ], mainly including the reduction of collagen and tissue extracellular matrix (ECM) components, which effectively resist external compression and maintain the ability of AF and NP tissues [ 12 , 13 ]. When the ECM is affected during the IDD process, the function of NP is extensively disrupted owing to reduced water storage, retention capacity, and nutrient transportation.…”
“…An increasing body of evidence suggests that despite their NP-specific differentiation potential and anti-inflammatory capacity, the intra-discal injection of “naked” MSCs is hampered by the harsh IDD microenvironment, resulting in poor survival rates, and altered activity [ [9] , [10] , [11] , [12] , [13] ]. PSCs are mainly restricted by the tumorigenesis risk, and their efficiency for NP-specific differentiation warrants more studies [ [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] ] (see Scheme 1 ). Scheme 1 General schematic of synthesis of esterase-responsive ibuprofen nano-micelles (PEG-PIB) to pre-modify embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) for synergistic transplantation in intervertebral disc degeneration.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
