Dynamic Cultivation of Mesenchymal Stem Cell Aggregates

Abstract

Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates.

Microcarriers for Upscaling Cultured Meat Production

“…Culture in aggregates consists in the formation of clumps of cells that grow in 3D and serve as anchors for their neighbors (21), whereas MCs are beads composed of various materials, porosities and topographies which provide a surface for anchorage-dependent cells to adhere to McKee and Chaudhry (22). Although very high achieved cell densities have been reported with aggregates (23)(24)(25) and in theory, a 3D environment closer to the native environment of the cells is provided, this technique offers little control of aggregates size, resulting in nutrients' and O 2 gradients inside the aggregates and necrotic cores (22,26). There are a few reports referring to the aggregate culture of myogenic cells (27)(28)(29).…”

A comparative study of the capacity of mesenchymal stromal cell lines to form spheroids

“…Furthermore, this model has also been tested as a surrogate niche for hematopoietic cells [17][18][19][20][21][22][23]. Spheroids take advantage of the ability of MSCs to self-aggregate, which is improved by using various approaches such as low adhesion plates, natural and artificial (centrifugation) gravity, cell matrix or more complex scaffolds [13,14,24,25]. Classically, studies have used human primary MSCs, from BM, cord blood and lipoaspirate, or rodent sources [15,26].…”

Intrinsic Cellular Responses of Human Wharton’s Jelly Mesenchymal Stem Cells Influenced by O2-Plasma-Modified and Unmodified Surface of Alkaline-Hydrolyzed 2D and 3D PCL Scaffolds

“…However, in a stressful environment, after initial seeding (such as growth on the stiffer ECM under lower ligand stimulation), alternative signaling via RhoA protein to control the cell cycle through regulation of cyclin proteins may occur [28,[30][31][32][33][34][35]. Recent reviews also indicated that the mesenchymal stem cells (MSCs) on 3D cultures may grow in the aggregated form, which can increase viability, proliferation, and paracrine effects by themselves [36]. Although there was no statistical difference between plasma-treated and non-plasma-treated scaffolds, slightly more FAK and cyclin A expressions can be observed on the plasma-treated and non-plasma-treated scaffolds, respectively (Figure 7).…”