ABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. The aim of this study is to establish an efficient method for the production of MSCs from pluripotent stem cells for potential clinical application in rare human disease Hutchinson-Gilford progeria syndrome. RESULTS: We established a robust method allowing rapid derivation of MSCs from both human iPSCs and ESCs via a temporal induction of neural ectoderm in chemically defined media. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. To evaluate the potential application of this method in disease modeling, MSCs were generated from iPSCs derived from a patient with Hutchinson-Gilford progeria syndrome (HGPS-MSCs) and from mutation-rectified HGPS-iPSCs (cHGPS-MSCs). HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs. CONCLUSIONS: The robust method of MSC derivation from ESCs and iPSCs provides an efficient approach to rapidly generate sufficient MSCs for in vitro disease modeling and clinical applications.
ABSTRACT
Isthmin (ISM) is a secreted protein family with two members, namely ISM1 and ISM2, both containing a TSR1 domain followed by an AMOP domain. Its broad expression pattern suggests diverse functions in developmental and physiological processes. Over the past few years, multiple studies have focused on the functional analysis of the ISM protein family in several events, including angiogenesis, metabolism, organ homeostasis, immunity, craniofacial development, and cancer. Even though ISM was identified two decades ago, we are still short of understanding the roles of the ISM protein family in embryonic development and other pathological processes. To address the role of ISM, functional studies have begun but unresolved issues remain. To elucidate the regulatory mechanism of ISM, it is crucial to determine its interactions with other ligands and receptors that lead to the activation of downstream signalling pathways. This review provides a perspective on the gene organization and evolution of the ISM family, their links with developmental and physiological functions, and key questions for the future.
