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Serum-free Growth Media Improves Mesenchymal Stem Cell Therapy for Chronic Kidney Disease

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Review of “Serum‐Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

While widespread in general laboratory practice, the requirement for serum-based growth media for the expansion of mesenchymal stem cells (MSCs) supposes several risks to their clinical application, including the transmission of viral diseases and unwanted immune reactions [1-3]. Furthermore, autologous human serum presents with problems related to the condition of the patient and the volumes required [4], while allogeneic human serum can promote growth arrest [5]. Therefore, the application of a fully defined serum-free media for MSC culture could circumnavigate these vexing problems and improve therapeutic outcomes for a range of diseases and disorders.

Researchers from the laboratories of Ayumu Nakashima and Takao Masaki (Hiroshima University, Japan) recently compared MSCs cultured in serum-containing and serum-free growth media with regards to their effects on inflammation and subsequent renal fibrosis in an experimental rat model of chronic kidney disease [6]. Yoshida et al. hope that their new STEM CELLS Translational Medicine study will path the way for the development of a more effective treatment for a condition that imposes substantial socioeconomic burdens to a multitude of patients around the globe [7].

This new study compared MSCs cultured in growth medium containing 10% fetal bovine serum to MSCs grown in STK2 serum‐free media (DS Pharma Biomedical, Osaka, Japan) containing various growth factors (such as FGF2, insulin, PDGF, and EGF), lipids (including fatty acids and phospholipids), nutrients, and minerals. Interestingly, initial in vitro analysis established that conditioned media derived from both MSCs cultured conditions suppressed transforming growth factor‐β1 (TGF β1) signaling in human kidney cells to a similar level, indicative of a similar direct anti-fibrotic effect [8]. 

However, in vivo analysis in an experimental rat model of chronic kidney disease provided immunohistochemical evidence that the administration of serum-free cultured MSCs suppressed inflammation and ameliorated renal fibrosis induced by unilateral ureteral obstruction to a greater extent. Mechanistically, serum-free conditions enhanced the ability of MSCs to suppression of inflammation via the elevated induction proinflammatory M1 macrophage polarization into immunosuppressive M2 macrophages and the heightened expression of tumor necrosis factor‐α–induced protein 6 (TSG‐6), which inhibits the recruitment of inflammatory cells.

The authors anticipate that their study will establish serum-free cultured MSCs as safe and effective means to reduce inflammation, inhibit fibrosis, and improve therapeutic outcomes in the many human patients suffering from chronic kidney disease across the globe.

For more on the advantages of serum-free growth conditions and more stem cell therapies for inflammation, renal fibrosis, and chronic kidney disease, stay tuned to the Stem Cells Portal.

References

  1. Perez-Ilzarbe M, Diez-Campelo M, Aranda P, et al., Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy. Transfusion 2009;49:1901-10.
  2. Nimura A, Muneta T, Koga H, et al., Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis & Rheumatology 2008;58:501-10.
  3. Shih DT and Burnouf T, Preparation, quality criteria, and properties of human blood platelet lysate supplements for ex vivo stem cell expansion. Nature Biotechnology 2015;32:199-211.
  4. Lanza D, Perna AF, Oliva A, et al., Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells. PLOS ONE 2015;10:e0116468.
  5. Shahdadfar A, Fronsdal K, Haug T, et al., In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. STEM CELLS 2005;23:1357-66.
  6. Yoshida K, Nakashima A, Doi S, et al., Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis. STEM CELLS Translational Medicine 2018;7:893-905.
  7. Jha V, Garcia-Garcia G, Iseki K, et al., Chronic kidney disease: global dimension and perspectives. Lancet 2013;382:260-72.
  8. Ueno T, Nakashima A, Doi S, et al., Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling. Kidney International 2013;84:297-307.