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Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell MSC Spheroids Primed in 3-D Cultures Under Xeno-free Conditions
Published on: March 18, 2017
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Increased Mesenchymal Stem Cell Functionalization in Three-Dimensional Manufacturing Settings for Enhanced
Dimitrios Kouroupis1,2, Diego Correa1,2
1Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL, United States.
Frontiers in Bioengineering and Biotechnology
|March 1, 2021
Summary
Three-dimensional (3D) culturing of mesenchymal stem/stromal cells (MSCs) in vitro overcomes limitations of traditional 2D expansion. This approach enhances MSC therapeutic potential and reproducibility for safer, more effective cell-based therapies.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Biotechnology
Background:
- Mesenchymal stem/stromal cells (MSCs) are crucial for regenerative medicine but exhibit variable stemness and function.
- Standard 2D in vitro expansion degrades MSC quality, leading to inconsistent therapeutic outcomes and manufacturing challenges.
- Existing methods like cell priming have limitations, including transient HLA-DR expression affecting allogeneic use.
Purpose of the Study:
- To review the functionalization of MSCs using 3D culturing techniques.
- To explore how 3D culture recapitulates the in vivo niche and enhances MSC properties.
- To discuss the potential of 3D MSC spheroids for improving cell-based therapies.
Main Methods:
- Review of in vitro and ex vivo techniques for MSC manufacturing.
- Analysis of 3D spheroid culture systems for MSCs.
- Evaluation of MSC spheroid characteristics, including phenotype, function, and in vivo performance.
Main Results:
- 3D MSC spheroids mimic in vivo niches, promoting enhanced cell-cell interactions and stable phenotypes.
- MSC spheroids exhibit increased trophic and immunomodulatory functions, alongside improved medicinal signaling.
- Preclinical studies demonstrate safety and efficacy of MSC spheroids in models of wound healing, bone defects, and cardiovascular diseases.
Conclusions:
- 3D MSC culturing offers a promising strategy to overcome limitations of 2D expansion.
- This approach can lead to more reproducible and effective MSC-based products.
- Incorporating 3D culture may reduce the need for ex vivo stimulatory regimes, enhancing therapeutic applications.

