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Mesenchymal Stem Cell Capping on ECM-Anchored Caspase Inhibitor-Loaded PLGA Microspheres for Intraperitoneal

Shiva Pathak1, Shobha Regmi1, Prakash Shrestha1

  • 1College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.

Small (Weinheim an Der Bergstrasse, Germany)
|April 25, 2019
PubMed

Insights

Mesenchymal stem cells (MSCs) show promise for inflammatory disorders, but poor survival hinders therapy. ECM-functionalized microspheres enhance MSC viability and function, offering a potential therapeutic advance.

Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Immunology

Background:

  • Mesenchymal stem cells (MSCs) are a promising therapeutic for inflammatory disorders.
  • Poor MSC viability and engraftment limit their clinical application.
  • Extracellular matrix (ECM)-coated scaffolds can improve MSC survival and integration.

Purpose of the Study:

  • To develop ECM-functionalized poly(lactic-co-glycolic acid) (PLGA) microspheres for enhanced MSC transplantation.
  • To evaluate the effect of ECM coating and caspase inhibition on MSC viability.
  • To assess the therapeutic efficacy of MSC-microsphere constructs in a murine colitis model.

Main Methods:

  • A single-step method for ECM functionalization of PLGA microspheres using dopamine-conjugated poly(ethylene-alt-maleic acid).
  • In vitro assessment of MSC viability on ECM-functionalized microspheres (eMs), with and without a caspase inhibitor (IDN6556).
  • In vivo evaluation of MSC-microsphere hybrid treatment in a murine model of experimental colitis.

Main Results:

  • ECM functionalization of PLGA microspheres (eMs) improved MSC viability.
  • Co-incorporation of a caspase inhibitor (IDN6556) synergistically enhanced in vitro MSC viability.
  • Intraperitoneal injection of MSC-microsphere hybrids reduced colitis severity by inhibiting Th1 and Th17 cell differentiation.

Conclusions:

  • ECM-functionalized microspheres offer a viable strategy to improve MSC survival and therapeutic potential.
  • Combining ECM coating with caspase inhibition further enhances MSC viability.
  • This approach holds promise for treating inflammatory diseases like colitis.
Keywords:
cell viabilitycolitisextracellular matrixmesenchymal stem cellstransplantation

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