Micromolding-based encapsulation of mesenchymal stromal cells in alginate for intraarticular injection in osteoarthritis

Nativel, Fabien; Smith, Audrey; Boulestreau, Jérémy; Lépine, Charles; Baron, Julie; Marquis, Mélanie; Vignes, Caroline; Guennec, Yoan Le; Véziers, Joëlle; Lesoeur, Julie; Loll, François; Halgand, Boris; Renard, Denis; Abadie, Jérôme; Legoff, Benoit; Blanchard, Frédéric; Gauthier, Olivier; Vinatier, Claire; Rieux, Anne des; Guicheux, Jérôme; Visage, Catherine Le

doi:10.1016/j.mtbio.2023.100581

Cited by 7 publications

(11 citation statements)

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“…Following the confirmation of the diffusion of some molecules of interest through these hydrogels, we investigated the ability of microencapsulated hASCs to secrete immunomodulatory factors in response to an inflammatory environment. The cells were exposed for 72 hours to pro-inflammatory factors, i.e., TNF-α and IFN-γ, as previously reported [21], [29]. The IDO activity and the concentration of PGE2 were significantly higher when the microencapsulated hASCs were treated with pro-inflammatory factors compared to the untreated microencapsulated cells.…”

Section: Discussionmentioning

confidence: 87%

“…In this study and for developing an OA cell therapy, it was crucial to generate micro-sized hydrogels to enable the intra-articular injection of alginate-based SPAAC hydrogels through a needle. We demonstrated the feasibility of producing alginate-based SPAAC microgels using the micromolding technique developed in our laboratory and previously used to micromold ionically cross-linked alginate hydrogels [21]. We have successfully generated microgels of cylindrical shape with reproducible size (average diameter of 166 µm) that were easily removed from the micromolds.…”

Section: Discussionmentioning

confidence: 99%

“…Hydrogel micromolding was executed using polydimethylsiloxane (PDMS) micromolds obtained via soft lithography, as previously described [21]. PDMS micromolds were sterilized in an autoclave and hydrophilized using O 2 plasma treatment (Zepto plasma system, Diener electronic; 40Watts, 90 s) immediately before use.…”

Section: Methodsmentioning

confidence: 99%

“…The secretory functions of microencapsulated hASCs were investigated as previously described, with minor modifications [21]. Microencapsulated cells (20,000 cells) were gradually deprived of FCS, starting at 10% on the day of encapsulation, decreasing to 5% on day 3, and further lowering to 2.5% on day 4.…”

Section: Secretory Activitymentioning

confidence: 99%

“…We then demonstrated the diffusion of molecules of interest through these hydrogels by a release monitoring method. Using a micromolding protocol developed in our laboratory [21], we successfully generated alginate- based SPAAC microgels with an average diameter of 170 µm. After confirming the feasibility of encapsulating hASCs in these alginate-based SPAAC microgels, we confirmed their cytocompatibility, with more than 90 % of cells remaining viable after 14 days of culture.…”

Section: Introductionmentioning

confidence: 99%

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Microencapsulation of mesenchymal stromal cells in covalent alginate hydrogels for cell therapy

Ambrosino,

Nativel,

Boyer

et al. 2023

Preprint

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Osteoarthritis (OA) is the most common inflammatory joint disease and currently lacks an effective curative treatment. Intra-articular injection of mesenchymal stromal cells (MSCs) has gained attention as a relevant therapeutic approach for OA treatment due to the MSC’s ability to secrete anti-inflammatory and immunomodulatory factors. Given their limited viability post-intraarticular injection and the potential leakage of cells out of the injection site, encapsulating MSCs in hydrogels is considered a promising strategy to protect them and provide a suitable 3D microenvironment to support their biological activities. Calcium-cross-linked alginate hydrogels are commonly used for MSC encapsulation, but their long-term in vivo stability remains uncertain. On the other hand, alginate cross-linking by the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction would create a network unaffected by an ionic environment. Hence, this study aimed to develop an alginate-based hydrogel cross-linked via stable and cytocompatible covalent bonds for cell encapsulation. We established for the first time the formation of covalent alginate hydrogels between two SPAAC precursors, namely alginate-BCN and alginate-N3. These hydrogels exhibited in vitro stability and enabled the diffusion of molecules of interest. We then generated alginate-based SPAAC microgels of 170 μm in mean diameter, suitable for intra-articular injection. We next encapsulated human adipose MSCs (hASCs) in these alginate-based SPAAC microgels and confirmed their cytocompatibility, with over 90 % of cells remaining viable after 14 days in culture. Finally, the microencapsulated hASCs maintained their biological properties and were able to secrete anti-inflammatory factors (IDO, PGE2, and HGF) when exposed to pro-inflammatory cytokines (TNF-α and IFN-γ). In the end, human activated lymphocytes were cultured in contact with microencapsulated hASCs, and CD3+ T cell proliferation was quantified by flow cytometry. We demonstrated that the encapsulation process did not impair the hASC immunomodulatory activity. Overall, our findings show the potential of alginate-based SPAAC hydrogels for microencapsulating hASCs for cell therapy.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Secretory Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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