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

间充质干细胞（MSC）是有望用作生物治疗药物的候选药物。由于局部注射的MSC在几周内消失，因此我们推测通过延长其存在可以增强MSC的功效。以前，建议将藻酸盐包封是用于此目的的合适方法。我们发现两种藻酸盐类型之间无差异，其中甘露糖醛酸含量高的藻酸盐（高M）和古拉糖醛酸含量高的藻酸盐（高G）在免疫活性大鼠皮下植入后的MSC活力，MSC免疫调节能力或胶囊完整性的保留方面。高G被证明更适合生产可注射的珠子。使用萤火虫荧光素酶表达的大鼠MSC追踪MSC的生存能力。封装在高G藻酸盐中可延长单碘乙酸酯诱导的骨关节炎的免疫能力大鼠中代谢活性同种异体MSC的存在至少持续8周。在这种疾病模型中，通过关节腔内注射进行局部治疗的人MSC封装并未显着影响对疼痛，滑膜炎症或软骨损伤的影响。海藻酸盐中的MSC封装允许采用可注射的方法，从而延长皮下或骨关节炎关节中活细胞的存在。为了提高治疗效果，可能需要对藻酸盐制剂和有效剂量进行进一步的微调，以取决于目标疾病。在这种疾病模型中，通过关节腔内注射进行局部治疗的人MSC封装并未显着影响对疼痛，滑膜炎症或软骨损伤的影响。海藻酸盐中的MSC封装允许采用可注射的方法，从而延长皮下或骨关节炎关节中活细胞的存在。为了提高治疗效果，可能需要对藻酸盐制剂和有效剂量进行进一步的微调，以取决于目标疾病。在这种疾病模型中，通过关节腔内注射进行局部治疗的人MSC封装并未显着影响对疼痛，滑膜炎症或软骨损伤的影响。海藻酸盐中的MSC封装允许采用可注射的方法，从而延长皮下或骨关节炎关节中活细胞的存在。为了提高治疗效果，可能需要对藻酸盐制剂和有效剂量进行进一步的微调，以取决于目标疾病。

图形概要