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Mammalian Cell Encapsulation in Alginate Beads Using a Simple Stirred Vessel
Published on: June 29, 2017
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.
Abstract:
Mesenchymal stem cells (MSC) are promising candidates for use as a biological therapeutic. Since locally injected MSC disappear within a few weeks, we hypothesize that efficacy of MSC can be enhanced by prolonging their presence. Previously, encapsulation in alginate was suggested as a suitable approach for this purpose. We found no differences between the two alginate types, alginate high in mannuronic acid (High M) and alginate high in guluronic acid (High G), regarding MSC viability, MSC immunomodulatory capability, or retention of capsule integrity after subcutaneous implantation in immune competent rats. High G proved to be more suitable for production of injectable beads. Firefly luciferase-expressing rat MSC were used to track MSC viability. Encapsulation in high G alginate prolonged the presence of metabolically active allogenic MSC in immune competent rats with monoiodoacetate-induced osteoarthritis for at least 8 weeks. Encapsulation of human MSC for local treatment by intra-articular injection did not significantly influence the effect on pain, synovial inflammation, or cartilage damage in this disease model. MSC encapsulation in alginate allows for an injectable approach which prolongs the presence of viable cells subcutaneously or in an osteoarthritic joint. Further fine tuning of alginate formulation and effective dosage for might be required in order to improve therapeutic efficacy depending on the target disease. Graphical Abstract.
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.

