MEDICINE

Tissue engineering and regenerative medicine: new frontiers for organ damage repair

What are stem cells?
Stem cells are undifferentiated cells capable of self-renewal that can differentiate into other types of cells. They cannot survive outside the environment without certain factors and cytokines. For example, unipotent stem cells cannot differentiate into as many cell types as pluripotent stem cells.1,2

Mechanism of Stemness
The developmental potential, or potency, of stem cells varies based on their specialty. Totipotent stem cells have the highest differentiation potential. Unlike pluripotent stem cells, totipotent stem cells can divide and differentiate into all cells that make up the entire organism, including both embryonic and extraembryonic structures. An example of a totipotent cell is a fertilized egg that develops after a sperm fertilizes an egg. When the totipotent zygote divides into more specialized cells, it forms a blastocyst containing pluripotent cells in an inner cell mass containing embryonic stem cells (ESCs).1,3

Human pluripotent stem cells give rise to all three primary germ layers during embryonic development. This means that they can develop into all cells of the adult body, but do not form extraembryonic structures such as the placenta.During embryogenesis, ESCs develop into ectoderm, mesoderm, or Differentiates into one of his three germ layers of endoderm. These layers produce differentiated cells and tissues. After embryogenesis, pluripotent stem cells also exist throughout the organism as undifferentiated cells. These cells proliferate to form the next generation of stem cells, which differentiate into specialized cells under specific physiological conditions.1,3 Conversely, the stem cell environment and certain stem cell factors can promote the dedifferentiation of specialized cells, reverting them to a primitive state of development or stemness.2

Flowchart showing developmental stages including fertilization, blastocyst formation, three germ layers, and specialized cells arising from each layer. The flowchart also shows the corresponding developmental potential at each stage, including totipotency, pluripotency, pluripotency, and unipotency. Embryonic transcription factor. Pluripotent stem cells and iPSCs function similarly, and the discovery of iPSCs has helped researchers understand how transcription factors influence cell differentiation during reprogramming and normal development. 1,3,4

The developmental potential of stem cells declines as they become more specialized. After fertilization, totipotent zygotes divide into more specialized cells and form blastocysts containing pluripotent ESCs in the inner cell mass. ESCs differentiate into one of three germ layers that generate differentiated cells and tissues in fetal and adult organisms.

How are researchers using pluripotent stem cells?
Pluripotent stem cells can self-renew indefinitely while maintaining the ability to differentiate into all cell types in vitro and in vivo. For this reason, researchers are using pluripotent stem cell lines to study early development. These cell lines are also a source of unspecialized cells with therapeutic potential. Scientists understand how pluripotent stem cells can be cultured and used for regenerative medicine, disease modeling, and drug discovery.1,3

Embryonic development studies
Pluripotent stem cell characteristics evolve as development progresses through embryogenesis, and different stages of this process are characterized by distinct cellular transcriptional and epigenetic signatures. During development, cells mature through a continuum of pluripotent states with unique properties that researchers can capture in vitro using stable pluripotent stem cell types. Furthermore, the discovery of iPSCs has shown that scientists can artificially alter cell fate by activating just a few transcription factors. This finding demonstrates an advanced researcher’s understanding of the epigenetic mechanisms that drive specialized cells into a differentiated state during development.3,4

Disease modeling with pluripotent stem cells
Scientists use human ESCs and iPSCs to generate a variety of disease-relevant cell types using differentiation protocols that mimic in vivo organogenesis. Therefore, researchers are using pluripotent stem cells to model disease with the aim of developing therapeutics. For example, iPSC-derived disease-specific stem cells are useful for studying degenerative diseases and gaining insight into diseases that lack adequate preclinical models. Scientists are also using pluripotent stem cells for disease modeling using organoids, stem cell-derived 3D structures, progenitor cells, and/or differentiated cells that self-assemble to recapitulate aspects of native tissue structure and function in vitro. apply.4,5

Regenerative medicine and drug discovery using patient-specific pluripotent stem cells
Regenerative medicine aims to restore the function of specific tissues in patients suffering from severe injuries or chronic diseases. Scientists are using disease-specific iPSCs to investigate the potential of stem cell transplantation to treat degenerative diseases. Furthermore, patient-specific pluripotent stem cells offer a promising platform for in vitro drug discovery and cell therapy. For example, the scientist will study her patient-derived iPSCs in vitro to investigate the impact of disease risk-associated mutations identified in genome-wide association studies (GWAS).4–6

References

  1. W. Zakrzewski et al., “Stem Cells: Past, Present and Future” Stem Cell Res Ther10:1-22, 2019.
  2. PM Aponte, A. Caicedo, “Cancer Stemness: Stem Cells, Cancer Stem Cells, and Their Microenvironment” Stem Cell Int2017: 1-17, 2017.
  3. S. Morgani et al., “Many Aspects of Pluripotency: In Vitro Adaptation to a Continuum of In Vivo Conditions,” BMC Dev Biol17:1-20, 2017.
  4. M. Stadtfeld, K. Hochedlinger, “Artificial Pluripotency: History, Mechanisms, and Applications” gene development24:2239-63, 2010.
  5. W. Hu, MA Lazar, “Modeling Metabolic Disease and Drug Response Using Stem Cells and Organoids” Nat Rev Endocrinols41574-022-00733-z, online before print, 2022.
  6. RS Mahla, “Stem Cell Applications in Regenerative Medicine and Disease Treatment,” Int J cell organism2016: 1-24, 2016.
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