Use of Encapsulated Stem Cells to Overcome the Bottleneck of Cell Availability for Cell Therapy Approaches

Abstract

Nowadays cell-based therapy is rarely in clinical practice because of the limited availability of appropriate cells. To apply cells therapeutically, they must not cause any immune response wherefore mainly autologous cells have been used up to now. The amount of vital cells in patients is limited, and under certain circumstances in highly degenerated tissues no vital cells are left. Moreover, the extraction of these cells is connected with additional surgery; also the expansion in vitro is difficult. Other approaches avoid these problems by using allo-or even xenogenic cells. These cells are more stable concerning their therapeutic behavior and can be produced in stock. To prevent an immune response caused by these cells, cell encapsulation (e.g. with alginate) can be performed. Certain studies showed that encapsulated allo-and xenogenic cells achieve promising results in treatment of several diseases. For such cell therapy approaches, stem cells, particularly mesenchymal stem cells, are an interesting cell source. This review deals on the one hand with the use of encapsulated cells, especially stem cells, in cell therapy and on the other hand with bioreactor systems for the expansion and differentiation of mesenchymal stem cells in reproducible and sufficient amounts for potential clinical use.

Mesenchymal Stem or Stromal Cells: Toward a Better Understanding of Their Biology?

“…Besides the biological availability of a highly specific single marker for the detection and isolation and expansion of MSCs, novel technologies are highly desired to expand MSCs in a relatively non-manipulated state on large scale for clinical proposes. This topic is depicted in more detail by Freimark et al [115] in this issue.…”

CELL DETACHMENT BY PROLYL-SPECIFIC ENDOPEPTIDASE FROM <i>WOLFIPORIA COCOS</i>

“…For example for hMSC-TERT ATMP production, it is not only important to efficiently detach cells, but also to keep them viable (and undifferentiated). This gets challenging when production takes places in dynamic systems (stirred tank reactors (Cierpka et al, 2013;Elseberg et al, 2012), fixed bed-systems (Weber et al, 2010a;2010b;2010c) and the harvested cells are further processed (e.g., beadto-bead transfer, cell encapsulation (Freimark et al, 2010). Trypsin is unsuitable for hMSC-TERT detachment out of dynamic systems and for detachment of further processed cells.…”

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

“…Various production methods have been tested to generate small beads (200-400 µm) with a narrow size distribution [119]. The formation of core capsules is often suggested [120] and this can be used to induce line-specific differentiation [22] even when cells are cultivated in a FBR [90]. Biopolymers such as agarose, Pluronic F-127 [121] and clinical-grade alginate are used for this purpose, the latter forming three-dimensional structures in the presence of multivalent cations.…”