http://www.cell.com/article/S1934590923001200/pdf

Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected. 

/pdf/hypoimmune-induced-pluripotent-stem-cells-survive-long-term-26d19o34.pdf

Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable to genetic engineering, and can be differentiated into most somatic cell types. iPSCs have been widely applied to model human development and diseases, perform drug screening, and develop cell therapies. In this review, we outline key developments in the iPSC field and highlight the immense versatility of the iPSC technology for in vitro modeling and therapeutic applications. We begin by discussing the pivotal discoveries that revealed the potential of a somatic cell nucleus for reprogramming and led to successful generation of iPSCs. We consider the molecular mechanisms and dynamics of somatic cell reprogramming as well as the numerous methods available to induce pluripotency. Subsequently, we discuss various iPSC-based cellular models, from mono-cultures of a single cell type to complex three-dimensional organoids, and how these models can be applied to elucidate the mechanisms of human development and diseases. We use examples of neurological disorders, coronavirus disease 2019 (COVID-19), and cancer to highlight the diversity of disease-specific phenotypes that can be modeled using iPSC-derived cells. We also consider how iPSC-derived cellular models can be used in high-throughput drug screening and drug toxicity studies. Finally, we discuss the process of developing autologous and allogeneic iPSC-based cell therapies and their potential to alleviate human diseases. 

Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming.

Insulin-producing β cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between β cells and awry enterochromaffin-like cells is a gradient of cell states rather than a stark difference in identity. Furthermore, transplantation of SC-islets in vivo improved cellular identities overtime, while long-term in vitro culture did not. Collectively, our results highlight the importance of chromatin and transcriptional landscapes during islet cell specification and maturation. 

https://www.nature.com/articles/s41556-023-01150-8.pdf

Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification

Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Geospatial data is usually organized and managed by Geodatabase(GDB) Technology. But GDB is not compatible with diversified forms of geographic data, a spatial data transfer standard is necessary. VCT is the vector of the geospatial data transfer format. Incompatible data formats can be converted to GDB by VCT which is transition data format. The conversion of data formats from VCT to GDB is the key to land resource database construction and resource sharing. The Data Format Conversion Optimization(DFCO) algorithm was proposed through dynamic index file based on secondary development platform of AE and C# by comparing the VCT and GDB data model. The DFCO algorithm realized the conversion of data formats from VCT to GDB so that more geospatial data formats can be compatible with land resource database. By using DFCO algorithm, cost of land resource database construction will be reduced and conversion efficiency of data formats will be improved.

Conversion Algorithm of Data Formats from VCT to GDB

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Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Conversion Algorithm of Data Formats from VCT to GDB