MSC encapsulation in alginate microcapsules prolongs survival after intra-articular injection, a longitudinal in vivo

Sohrab Khatab1,2, Maarten J Leijs1,2, Gerben van Buul1

  • 1Department of Orthopaedics, Erasmus MC University Medical Center Rotterdam, Wytemaweg 80, 3015, CN, Rotterdam, the Netherlands.

Insights

Encapsulating mesenchymal stem cells (MSC) in alginate prolongs their presence for therapeutic use. High-guluronic acid alginate is ideal for injectable MSC delivery, enhancing cell viability in osteoarthritis models.

Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Stem Cell Therapy

Background:

  • Mesenchymal stem cells (MSC) show therapeutic potential but have short in vivo lifespans.
  • Prolonging MSC presence is crucial for enhancing therapeutic efficacy.
  • Alginate encapsulation is a potential strategy to extend MSC survival.

Purpose of the Study:

  • To evaluate alginate encapsulation for prolonging MSC viability and therapeutic effects.
  • To compare high-mannuronic acid (High M) and high-guluronic acid (High G) alginate for MSC encapsulation.
  • To assess the impact of encapsulated MSC on an osteoarthritis disease model.

Main Methods:

  • MSC viability, immunomodulatory capacity, and capsule integrity were assessed in vitro and in vivo.
  • High M and High G alginate beads were compared for subcutaneous implantation in rats.
  • Firefly luciferase-expressing rat MSC were used to track cell viability in an osteoarthritis model.
  • Encapsulated human MSC were administered via intra-articular injection in the osteoarthritis model.

Main Results:

  • No significant differences were observed between High M and High G alginate regarding MSC viability, immunomodulatory capacity, or capsule integrity.
  • High G alginate was more suitable for producing injectable beads.
  • Encapsulation in High G alginate significantly prolonged the presence of metabolically active allogeneic MSC for at least 8 weeks in an osteoarthritis model.
  • Intra-articular injection of encapsulated human MSC did not significantly improve pain, synovial inflammation, or cartilage damage in the osteoarthritis model.

Conclusions:

  • Alginate encapsulation provides an injectable method to prolong the presence of viable MSC, both subcutaneously and within an osteoarthritic joint.
  • High G alginate is a suitable material for injectable MSC delivery.
  • Further optimization of alginate formulation and dosage is necessary to enhance therapeutic efficacy for specific diseases.

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