Affiliation:
1. Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, United States
Abstract
:
Embryonic stem cells (ESCs) are stem cells (SCs) that can self-renew and differentiate into a
myriad of cell types. The process of developing stemness is determined by signaling molecules that drive
stem cells to a specific lineage. For example, ESCs can differentiate into mature cells (e.g., cardiomyocytes)
and mature cardiomyocytes can be characterized for cell beating, action potential, and ion channel
function. A goal of this Perspective is to show how small molecules can be used to differentiate ESCs into
cardiomyocytes and how this can reveal novel aspects of SC biology. This approach can also lead to the
discovery of new molecules of use in cardiovascular disease.
:
Human induced pluripotent stem cells (hiPSCs) afford the ability to produce unlimited numbers of normal
human cells. The creation of patient-specific hiPSCs provides an opportunity to study cell models of human
disease. The second goal is to show that small molecules can stimulate hiPSC commitment to cardiomyocytes.
How iPSCs can be used in an approach to discover new molecules of use in cardiovascular
disease will also be shown in this study.
:
Adult SCs, including mesenchymal stem cells (MSCs), can likewise participate in self-renewal and multilineage
differentiation. MSCs are capable of differentiating into osteoblasts, adipocytes or chondrocytes.
A third goal of this Perspective is to describe differentiation of MSCs into chondrogenic and osteogenic
lineages. Small molecules can stimulate MSCs to specific cell fate both in vitro and in vivo. In this Perspective,
some recent examples of applying small molecules for osteogenic and chondrogenic cell fate
determination are summarized. Underlying molecular mechanisms and signaling pathways involved are
described. Small molecule-based modulation of stem cells shows insight into cell regulation and potential
approaches to therapeutic strategies for MSC-related diseases.
Funder
California Institute for Regenerative Medicine
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,General Medicine