Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.

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Human mesenchymal stem cells possess different biological characteristics but do not change their therapeutic potential when cultured in serum free medium

Stem Cell Research & Therapy ◽

10.1186/scrt522 ◽

2014 ◽

Vol 5 (6) ◽

pp. 132 ◽

Cited By ~ 16

Author(s):

Youwei Wang ◽

Hehe Wu ◽

Zhouxin Yang ◽

Ying Chi ◽

Lei Meng ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Human Mesenchymal Stem Cells ◽

Biological Characteristics ◽

Serum Free Medium ◽

Free Medium ◽

Serum Free

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Development of a process control strategy for the serum-free microcarrier expansion of human mesenchymal stem cells towards cost-effective and commercially viable manufacturing

Biochemical Engineering Journal ◽

10.1016/j.bej.2018.10.018 ◽

2019 ◽

Vol 141 ◽

pp. 200-209 ◽

Cited By ~ 6

Author(s):

Thomas R.J. Heathman ◽

Alvin W. Nienow ◽

Qasim A. Rafiq ◽

Karen Coopman ◽

Bo Kara ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Process Control ◽

Control Strategy ◽

Human Mesenchymal Stem Cells ◽

Cost Effective ◽

Serum Free

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A Microarray Analysis of the Effects of Serum-free Medium on Gene Expression Changes in Human Mesenchymal Stem Cells during the in Vitro Culture

YAKUGAKU ZASSHI ◽

10.1248/yakushi.130.1387 ◽

2010 ◽

Vol 130 (10) ◽

pp. 1387-1393 ◽

Cited By ~ 5

Author(s):

Rumi SAWADA ◽

Takashi YAMADA ◽

Toshie TSUCHIYA ◽

Atsuko MATSUOKA

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

In Vitro Culture ◽

Microarray Analysis ◽

Human Mesenchymal Stem Cells ◽

Serum Free Medium ◽

Free Medium ◽

Serum Free

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Human Mesenchymal Stem Cells Display Reduced Expression of CD105 after Culture in Serum-Free Medium

Stem Cells International ◽

10.1155/2013/698076 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 46

Author(s):

Peter Mark ◽

Mandy Kleinsorge ◽

Ralf Gaebel ◽

Cornelia A. Lux ◽

Anita Toelk ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ex Vivo ◽

Human Mesenchymal Stem Cells ◽

Cell Types ◽

Growth Media ◽

Clinical Use ◽

Differentiation Potential ◽

Serum Free ◽

The Impact

Human Mesenchymal Stem Cells (hMSCs) present a promising tool for regenerative medicine. However,ex vivoexpansion is necessary to obtain sufficient cells for clinical therapy. Conventional growth media usually contain the critical component fetal bovine serum. For clinical use, chemically defined media will be required. In this study, the capability of two commercial, chemically defined, serum-free hMSC growth media (MSCGM-CD and PowerStem) for hMSC proliferation was examined and compared to serum-containing medium (MSCGM). Immunophenotyping of hMSCs was performed using flow cytometry, and they were tested for their ability to differentiate into a variety of cell types. Although the morphology of hMSCs cultured in the different media differed, immunophenotyping displayed similar marker patterns (high expression of CD29, CD44, CD73, and CD90 cell surface markers and absence of CD45). Interestingly, the expression of CD105 was significantly lower for hMSCs cultured in MSCGM-CD compared to MSCGM. Both groups maintained mesenchymal multilineage differentiation potential. In conclusion, the serum-free growth medium is suitable for hMSC culture and comparable to its serum-containing counterpart. As the expression of CD105 has been shown to positively influence hMSC cardiac regenerative potential, the impact of CD105 expression onto clinical use after expansion in MSCGM-CD will have to be tested.

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Human mesenchymal stem cells from the umbilical cord matrix: Successful isolation and ex vivo expansion using serum-/xeno-free culture media

Biotechnology Journal ◽

10.1002/biot.201200340 ◽

2013 ◽

Vol 8 (4) ◽

pp. 448-458 ◽

Cited By ~ 35

Author(s):

Irina N. Simões ◽

Joana S. Boura ◽

Francisco dos Santos ◽

Pedro Z. Andrade ◽

Carla M. P. Cardoso ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Culture Media ◽

Ex Vivo ◽

Human Mesenchymal Stem Cells ◽

Ex Vivo Expansion ◽

Successful Isolation ◽

Umbilical Cord Matrix

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Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.642681 ◽

2021 ◽

Vol 9 ◽

Author(s):

Thora Bjorg Sigmarsdottir ◽

Sarah McGarrity ◽

James T. Yurkovich ◽

Óttar Rolfsson ◽

Ólafur Eysteinn Sigurjónsson

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Cell Lineage ◽

Human Mesenchymal Stem Cells ◽

Metabolic Model ◽

Metabolic Function ◽

Metabolic States ◽

Initial Discovery ◽

Genome Scale

Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs.

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