Dataset Information

Lens regeneration in situ using hESCs-derived cells -similar to natural lens.

ABSTRACT: Lens itself has limited regeneration functionality, thus we aimed to create regenerated lens with biological function to treat cataracts rather than the intraocular lens used in cataract surgery. We induced exogenous human embryonic stem cells to directionally differentiate into lens fate like cells in vitro, mixed these cells with hyaluronate, and then implanted the mixture into lens capsule to regenerate in vivo. We successfully achieved near-complete lens regeneration, and the thickness of the regenerated lens reached 85% of the contralateral eye, showing the characteristics of biconvex shape, transparency, and a thickness and diopter close to that of natural lenses. Meanwhile, the participation of Wnt/PCP pathway in lens regeneration was verified. The regenerated lens in this study was the most transparent, thickest, and most similar to the original natural lens that has thus far been reported. Overall, these findings offer a new therapeutic strategy for cataracts and other lens diseases.

SUBMITTER: Chen X

PROVIDER: S-EPMC10291466 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lens regeneration in situ using hESCs-derived cells -similar to natural lens.

Chen Xinyi X Wang Hanle H Chen Hui H Ren Ling L Wang Wei W Xu Jingjie J Luo Chenqi C Hu Peike P Fu Qiuli Q Yao Ke K

iScience 20230519 6

Lens itself has limited regeneration functionality, thus we aimed to create regenerated lens with biological function to treat cataracts rather than the intraocular lens used in cataract surgery. We induced exogenous human embryonic stem cells to directionally differentiate into lens fate like cells in vitro, mixed these cells with hyaluronate, and then implanted the mixture into lens capsule to regenerate in vivo. We successfully achieved near-complete lens regeneration, and the t ...[more]

PMID: 37378332

Similar Datasets

Project description:The crystalline lens is an important optic element in human eyes. It is transparent and biconvex, refracting light and accommodating to form a clear retinal image. The lens originates from the embryonic ectoderm. The epithelial cells at the lens equator proliferate, elongate and differentiate into highly aligned lens fiber cells, which are the structural basis for maintaining the transparency of the lens. Cataract refers to the opacity of the lens. Currently, the treatment of cataract is to remove the opaque lens and implant an intraocular lens (IOL). This strategy is inappropriate for children younger than 2 years, because a developing eyeball is prone to have severe complications such as inflammatory proliferation and secondary glaucoma. On the other hand, the absence of the crystalline lens greatly affects visual function rehabilitation. The researchers found that mammalian lenses possess regenerative potential. We identified lens stem cells through linear tracking experiments and designed a minimally invasive lens-content removal surgery (MILS) to remove the opaque lens material while preserving the lens capsule, stem cells and microenvironment. In infants with congenital cataract, functional lens regeneration in situ can be observed after MILS, and the prognosis of visual function is better than that of traditional surgery. Because of insufficient regenerative ability in humans, the morphology and volume of the regenerated lens cannot reach the level of a normal lens. The activation, proliferation and differentiation of lens stem cells and the alignment of lens fibers are regulated by epigenetic factors, growth factors, transcription factors, immune system and other signals and their interactions. The construction of appropriate microenvironment can accelerate lens regeneration and improve its morphology. The therapeutic concept of MILS combined with microenvironment manipulation to activate endogenous stem cells for functional regeneration of organs in situ can be extended to other tissues and organs with strong self-renewal and repair ability.

Project description:BackgroundMesenchymal stem cells (MSCs) are known to have different differentiation potential depending on the tissue of origin. Dedifferentiated fat cells (DFATs) are MSC-like multipotent cells that can be prepared from mature adipocytes by ceiling culture method. It is still unknown whether DFATs derived from adipocytes in different tissue showed different phenotype and functional properties. In the present study, we prepared bone marrow (BM)-derived DFATs (BM-DFATs), BM-MSCs, subcutaneous (SC) adipose tissue-derived DFATs (SC-DFATs), and adipose tissue-derived stem cells (ASCs) from donor-matched tissue samples. Then, we compared their phenotypes and multilineage differentiation potential in vitro. We also evaluated in vivo bone regeneration ability of these cells using a mouse femoral fracture model.MethodsBM-DFATs, SC-DFATs, BM-MSCs, and ASCs were prepared from tissue samples of knee osteoarthritis patients who received total knee arthroplasty. Cell surface antigens, gene expression profile, and in vitro differentiation capacity of these cells were determined. In vivo bone regenerative ability of these cells was evaluated by micro-computed tomography imaging at 28 days after local injection of the cells with peptide hydrogel (PHG) in the femoral fracture model in severe combined immunodeficiency mice.ResultsBM-DFATs were successfully generated at similar efficiency as SC-DFATs. Cell surface antigen and gene expression profiles of BM-DFATs were similar to those of BM-MSCs, whereas these profiles of SC-DFATs were similar to those of ASCs. In vitro differentiation analysis revealed that BM-DFATs and BM-MSCs had higher differentiation tendency toward osteoblasts and lower differentiation tendency toward adipocytes compared to SC-DFATs and ASCs. Transplantation of BM-DFATs and BM-MSCs with PHG enhanced bone mineral density at the injection sites compared to PHG alone in the mouse femoral fracture model.ConclusionsWe showed that phenotypic characteristics of BM-DFATs were similar to those of BM-MSCs. BM-DFATs exhibited higher osteogenic differentiation potential and bone regenerative ability compared to SC-DFATs and ASCs. These results suggest that BM-DFATs may be suitable sources of cell-based therapies for patients with nonunion bone fracture.

Dataset Information

Lens regeneration in situ using hESCs-derived cells -similar to natural lens.

Publications

Lens regeneration <i>in situ</i> using hESCs-derived cells -similar to natural lens.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets