In Vivo Regeneration of Rat Laryngeal Cartilage with Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells Via Neural Crest Cells

Abstract

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

Self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids

“…mesoderm-derived articular cartilaginous tissues and the MTO cartilage resembles fetal limb bud and growth plate chondrocytes. Despite previous reports of hyaline cartilage appearance facilitated by chondrogenic induction of hiPSC in vitro [5][6][7][8] , MTO-generated cartilage stands out as they are larger, more mature, and can be maintained in long-term cultures. This process was also self-organized with a comparably simpler, xeno-and feeder-free, 3D culturing protocol, making production easily adaptable to cGMP production and amenable to scaled-up commercial manufacturing.…”

“…Regardless, neural crest cells (NCC) may have emerged from neural tube-like structures present in CO, which later spontaneously formed mesodermal derivatives, such as chondrocytes. Induction of chondrocytes from hiPSC through NCC intermediates has been recently reported by two independent groups 5,7 . Moreover, RNA-seq of MTOs agreed with the phenotypic transition of MTOs from week 8 to week 15, where we observed favored BMP pathway signaling and increased mesodermal processes associated with cartilage production.…”

“…Specifically, human induced pluripotent stem cells (hiPSC) have been shown to have the potential to differentiate into chondrocytes; however, clinical translation of hiPSC derived chondrocytes still faces several challenges. The common approach for generating hiPSC-derived chondrocytes has been a 2D-3D sequential culture where hiPSC-derived mesodermal cells are cultured in monolayer before 3D-such as pellet [4][5][6][7] and suspension 8,9 -cell culture. Implementing 3D culturing in the process has been shown to improve the quality of the cartilage generated 10 .…”

Dental applications of induced pluripotent stem cells and their derivatives

“…Established protocols have been reported for the efficient generation of MSCs from iNCCs. In studies, MSC media with or without supplements were used to induce MSCs from iNCCs [71] , [72] . LNGFR + THY-1 + NCLCs derived from hESC and hiPSCs had similar potential as MSCs to differentiate into mesenchymal lineages [73] .…”

“…The iNCCs-derived MSC-like cells (iNCMSCs) that our group generated exhibited homogenous character and osteochondral differentiation in vitro, although they did not restore the osteochondral defects in rats [71] . However, in another study, thyroid cartilage was generated by transplanting clumps consisting of iMSCs via iNCCs intermediates and extracellular matrix complex into immunodeficient rats [72] . iMSCs may be promising cell sources for bone and cartilage regeneration with optimized induction conditions.…”