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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Construction and Use of an Electrical Stimulation Chamber for Enhancing Osteogenic Differentiation in Mesenchymal Stem/Stromal Cells In Vitro
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Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation.

Angelo S Mao1,2, Berna Özkale1,2, Nisarg J Shah1,2,3

  • 1John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Proceedings of the National Academy of Sciences of the United States of America
|July 18, 2019
PubMed
Summary
This summary is machine-generated.

Biomaterial encapsulation improves mesenchymal stem cell (MSC) therapy by increasing cell survival and therapeutic potential. This method enhances MSC persistence and immunomodulatory capacity for treating immune dysregulation diseases.

Keywords:
MSCbiomaterialsimmune modulationmicrofluidicsregenerative medicine

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Regenerative Medicine

Background:

  • Mesenchymal stem cell (MSC) therapies show potential for immune dysregulation but face challenges with short in vivo cell persistence and inconsistent phenotypes.
  • Improving the survival and efficacy of MSCs is crucial for advancing their therapeutic applications.

Purpose of the Study:

  • To investigate the use of microfluidic-based alginate encapsulation to enhance in vivo persistence and immunomodulatory capacity of MSCs.
  • To assess the impact of encapsulation and cytokine licensing on MSC survival and therapeutic outcomes.

Main Methods:

  • Mesenchymal stem cells (MSCs) were encapsulated into alginate microgels using a microfluidic device.
  • Encapsulated MSCs were further modified through cell clustering and polylysine cross-linking.
  • Pretransplantation licensing with inflammatory cytokines was performed on encapsulated MSCs.
  • In vivo persistence was evaluated after intravenous injection, and immunomodulatory capacity was assessed by observing blood and bone marrow repopulation post-irradiation.

Main Results:

  • Alginate microgel encapsulation significantly increased the in vivo half-life of injected MSCs by over an order of magnitude.
  • Encapsulated MSCs exhibited prolonged persistence despite innate and adaptive immune responses.
  • Cytokine licensing of encapsulated MSCs upregulated immunomodulatory gene expression.
  • Licensed encapsulated MSCs promoted a twofold increase in allogeneic donor cell repopulation in recipient blood and bone marrow.

Conclusions:

  • Microgel encapsulation is an effective strategy to enhance mesenchymal stem cell (MSC) survival and persistence in vivo.
  • This approach improves the immunomodulatory capacity of MSCs, offering potential for more effective cell-based therapies.
  • Encapsulation technology holds promise for overcoming key limitations in current MSC therapeutic strategies.