Table 1 Summary and classification of the 14 articles selected from the database search
From: Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review
| Â | Author | Sample source | Application | Microcarrier used | Culture media used | Result | Conclusion |
|---|---|---|---|---|---|---|---|
1 | Chui et al. [51] | Human MSCs-hTERT cell line | MSC expansion | Electrosprayed genipin cross-linked alginate-chitosan microcarrier Cytodex 1 | Low glucose DMEM + 10% FBS | MSCs cultured on fabricated microcarriers had a 26% higher cell attachment and twice the proliferation rate compared to the commercial microcarrier No significant difference in gene expression between the two microcarriers for the positive MSC surface markers as well as showing either low or no signal for negative MSC surface markers | Genipin cross- linked alginate–chitosan based microcarriers can act as a potential alternative to commercial microcarriers for MSC expansion |
2 | Gupta et al. [60] | Human periosteum-derived cells | MSC Bone forming potential | Cultispher S | High glucose DMEM + 10% FBS/HPL | HPL resulted in faster cell proliferation compared to FBS Cell viability and trilineage differentiation capability were that maintained by HPL, although a suppression of adipogenic differentiation potential was observed HPL supplementation resulting in almost three times more mineralized tissue within calcium phosphate scaffolds | The use of HPL in bioreactor-based expansion of hPDCs is an optimal solution that increases expansion efficiency along with promoting bone forming capacity of these cells |
3 | Krutty et al. [59] | Bone marrow MSC | MSC expansion | PNIPAM grafted microcarriers | MEM α + 10% FBS | The microcarriers create a reproducible surface that does not rely on the adsorption of xenogenic serum proteins to mediate cell adhesion MSCs cultured on this fabricated microcarriers achieve sixfold expansion and retain their ability to differentiate after harvesting | PNIPAM grafted microcarriers are a relevant platform for expanding cells while maintaining hMSC functionality |
4 | Tanimowo Aiyelabegan et al. [57] | Rat bone marrow MSC | MSC osteogenic differentiation | k-casein conjugated agarose microspheres | DMEM | The cell viability of the synthesized microspheres significantly different from uncoated microspheres, but similar to the control and commercial microcarriers This microcarrier systems upregulated the expression of osteo- genic differentiation markers on bone marrow mesenchymal stem cells cultured on the carrier systems | k-casein conjugated agarose microspheres culturing environment may assist in reducing the need for expensive hormones and growth factors that directs differentiation, and thus, could reduce the risk of unwanted systemic side effects in vivo and aid the clinical translatability of MSCs that are cultured using this strategy for bone TE |
5 | Heathman et al. [63] | Bone marrow MSC | MSC expansion | Plastic P-102L microcarriers | PRIME-XV MSC Expansion SFM | It was found that growth rate though an intermediate value of ~ 1.3 NJS did not cause sampling difficulties, clumping and poor growth. At this range of agitation intensities, cell quality remained unchanged post-harvest Direct aeration of the culture medium both with and without Pluronic F68 via a sparger at NJS was detrimental to BM-hMSC growth | Alternative methods of supplying sufficient levels of oxygen to microcarrier bioreactor systems culturing BM-hMSCs may have to be developed as well as establishing the level of pCO2 that they can tolerate as these systems are scaled up to manufacture commercially-viable cell numbers |
6 | Yuan et al. [62] | Bone marrow MSC | MSC expansion | PNIPAM grafted microcarriers | MEM α + 10% FBS | hMSC aggregates generated from the bioreactor maintained comparable immunomodulation and cytokine secretion properties compared to the ones made from the culture plate At room temperature, hMSCs were self-assembled into 3D hMSC aggregates in PBS-VW bioreactor and remain as single cells in bioreactor owing to different hydrodynamic conditions | Thermal responsive microcarriers could scale-up the production of hMSC aggregates in the suspension bioreactor for integrated cell expansion |
7 | Dias et al. [58] | hMSC (Lonza, Walkersville, MD) | Serum-free MSC expansion | PEG-based hydrogel coated Hillex II amine-functionalized microcarriers | MEM α + 10% FBS Lonza serum-free MSC growth media | High cell expansion was apparent in serum-free media on coated microcarriers with some aggregation during expansion Osteoblast and adipocytes differentiation apparent in serum-free condition on PEG | The PEG hydrogel coating reduced microcarrier aggregation during MSC culture |
8 | Lin et al. [69] | Fetal bone marrow MSC | hMSC-microcarrier constructs chondrogenic differentiation | Cytodex 1 Cytodex 3 SphereCol Cultispher-S | MEM α + 10% FBS | Narrow range of 70% cell confluency, cell number of 10 x 10^3, and microcarrier of 300 per construct generate the optimal microenvironment for efficient chondrogenic differentiation | Scalable microcarrier-spinner cultures enhance the chondrogenic potential of the MSC, supporting their use for large-scale cell expansion in cartilage cell therapy |
9 | Rafiq et al. [61] | Bone marrow MSC (Lonza, Walkersville, MD) | Automated hMSC expansion | Plastic P102-L microcarrier | DMEM + 10% FBS PRIME-XV MSC Expansion SFM | More than 250% increase in yield compared to the serum-based process The combination of both serum-free and automated processing improved the reproducibility more than tenfold compared to the serum-based, manual spinner flask process | Ambr15 microbioreactor is an effective tool for bioprocess development of hMSC microcarrier cultures and improves both process yield and consistency. |
10 | Takahashi et al. [70] | Bone marrow MSC | MSC expansion | Cytodex 1 | Low glucose DMEM + 10% FCS | 30 rpm was the lowest agitation rate necessary for the suspension of Cytodex 1 microcarriers, and the cells grew fastest at 60 rpm The percentages of CD90- and CD166-positive cells among cells grown on Cytodex 1 at 60 rpm (91.5 and 87.6%) were comparable to those of cells grown in the pre-culture on dishes | Beads-to-beads subcultivation method maintaining the expressions of the cell surface antigens CD90 and CD166, while adjusting agitation rate could decrease the microcarrier aggregation |
11 | Zhang et al. [71] | Human amniotic MSC HUVEC | Pre-vascularized modular bone tissue fabrication | CultiSpher S | DMEM + 10% FBS MEM α + 10% FBS | Microtissues were formed with high cellularity after 4 weeks culture in spinner flask, evenly distributed cells and tube formation ability Coculture with HUVECs exerted an inhibitory effect on osteogenic differentiation of MSCs | An effective method to fabricate pre-vascularized bone microtissues was established, which would lay a solid foundation for subsequent development of vascularized tissue grafts for bone regeneration |
12 | Nienow et al. [54] | Bone marrow MSC | MSC expansion | Solohill plastic Solohill collagen | DMEM + 10% FBS | hMSCs were successfully cultured using the minimum agitator speed required for complete microcarrier suspension The cells were shown to retain their desired quality attributes and were able to proliferate with the reported cell detachment protocol | Theagitation strategy with respect to culture and harvest therefore offers a sound basis for a wide range of scales of operation |
13 | Song et al.[56] | Bone marrow MSC | MSC expansion | Thermosensitive glass microcarrier | Low glucose DMEM + 10% FBS | NIPAAm was successfully grafted on to the surface of the microcarriers, providing an excellent biocompatible environment for BMMSC adhesion and growth BMMSCs could be fully removed from the thermosensitive glass microcarriers with remained cell viability | This new substrate can provide a better 3D environment for cell growth and cell recovery, which is expected to be utilized in vitro for massive cell expansion by combining with the dynamic bioreactor |
14 | Lakhkar et al. [55] | hMSCs MG63 osteoblast-type cells | MSC Oesteogenic induction | Titanium phosphate glass microcarrier | Low glucose DMEM + 10% FCS | The microcarrier proliferative capacity is increasing in MG63 cell Expression of bone morphogenetic protein-2 and osteopontin, significantly greater Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces | The titanium phosphate glass microcarrier function as platforms for guided osteogenic differentiation of hMSCs. It is expected that these approaches will in future facilitate the development of viable bone tissue in vitro for use in bone replacement therapies |