Characterization of adipose‐derived stromal/stem cell spheroids versus single‐cell suspension in cell survival and arrest of osteoarthritis progression

Abstract

The current study evaluated the hypothesis that the administration of spheroidal adipose‐derived stromal/stem cells (ASCs) promotes cell survival and arrests the progression of surgically induced osteoarthritis (OA) in a rat model. We also tested the optimal conditions for spheroid production from ASCs using microwell methods. The formation of ASC spheroids was optimized at a well diameter of 600 μm under cell concentrations of 106cell/ml. When ASC spheroids cultured in 3D were compared with ASCs cultured in 2D monolayer, the cell survival and chondrogenic potential were enhanced while the apoptosis was reduced in ASC spheroids compared with ASCs in 2D monolayer culture. In vivo tracking of fluorescently labeled ASCs in the knee joints of rats with surgically induced OA showed longer fluorescent activity at a higher intensity in ASC spheroids than in ASC single‐cell suspension. When OA‐induced rats treated with ASC injection were sacrificed after 8 weeks, the OARSI score was enhanced in both ASC single‐cell suspension and ASC spheroids compared with negative control, spheroid treatment resulting in a better score than single‐cell treatment. However, injected cells were not detectable from the joints. These finding altogether suggests that ASC spheroids have better in vitro and in vivo survival and chondrogenic potential and exert greater regenerative effects for articular cartilage and arrest the progression of surgically induced OA better than ASCs in single‐cell suspension by the paracrine mode of action. The study findings support the notion of developing cell therapeutics to treat OA based on ASC spheroid forms.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

“…Three studies evaluated the injection of microencapsulated ASCs aggregated into spheroids, all showing improved chondroprotective effects and pain relief compared to ASCs alone [36][37][38].…”

Systematic review on spheroids from adipose‐derived stem cells: Spontaneous or artefact state?

“…Based on mechanical structure or new systems, several innovative techniques were developed to form spheroids of ASC characterized by controlled size, higher stemness, and improved differentiation abilities, such as the following: a method defined “all‐in‐one platform” with hydrogels with an embossed surface (HES) or lotus seedpod‐inspired (LoSH) (S. J. Kim, Park, Byun, et al, 2019; S. J. Kim, Park, Kim, et al, 2019); StemFit 3D, based on a 389‐microwell plate employed with gelatin microparticles (GMP) (Y. Kim, Baipaywad et al, 2018; Ko et al, 2020); microfabricated porous tissue strands (pTS) (Y. Wu et al, 2018); human dermis named thin sectioned acellular dermal matrix (tsADM) (J. H. Kim & Lee, 2020), lockyballs: microscaffolds with a porous wall and interlockable hooks produced by using two‐photon polymerization (Silva et al, 2016); CellSaic platform, based on a biodegradable material, a recombinant Recombinant protein (Iwazawa et al, 2018); MicoCell, a plate with bland adhesive properties, due to a fluorinated polyimide film (Shima & Makino, 2020). …”

Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing® and the Lethal Damage Sensitivity to Synovial Fluid In Vitro

“…Zhang et al showed that spheroid formation activates anti-inflammatory, anti-apoptotic, and angiogenic effects, as well as homing to the damaged site [35]. Ko et al compared ADSC spheroid and single-cell suspension viability and cartilage regeneration in an OA mouse model; the ADSC spheroid-treated group showed improved intra-articular cell viability and a significant OARSI score improvement, indicating the superiority of spheroids [54].…”