Serum-free media formulations are cell line–specific and require optimization for microcarrier culture

Tan, Kah Yong; Teo, Kim Leng; Lim, J.; Chen, Allen K.L.; Reuveny, Shaul; Oh, Steve

doi:10.1016/j.jcyt.2015.05.001

Cited by 45 publications

(37 citation statements)

References 71 publications

(50 reference statements)

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“…Excluded studies (10,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) and reasons are described in Table 4. Most of the included studies described protocols relying on the platelets lyse after freeze-thaw cycles to obtain VBDs.…”

Section: Resultsmentioning

confidence: 99%

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

et al. 2017

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Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse Scopus TM , PubMed, Web of Science TM , BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O' Malley's framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS's fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.

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Section: Resultsmentioning

confidence: 99%

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

et al. 2017

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“…To our knowledge, the comparison of microcarriers has only been performed in static mode for WJ‐MSC cultures in a hPL‐supplemented medium. However, it was previously demonstrated that MSC growth in stirred systems was not necessarily correlated to the growth in static microcarrier culture, and that early cell attachment and spreading on microcarriers was not necessarily representative of the efficiency of MSC expansion in agitated microcarrier cultures …”

Section: Introductionmentioning

confidence: 99%

“…However, it was previously demonstrated that MSC growth in stirred systems was not necessarily correlated to the growth in static microcarrier culture, and that early cell attachment and spreading on microcarriers was not necessarily representative of the efficiency of MSC expansion in agitated microcarrier cultures. 38 The objective of the present study was to determine a standardized method to cultivate WJ-MSC on microcarriers in a serum-free culture medium, supplemented with hPL. To do that, five animal product-free microcarriers were compared, both in static and dynamic modes.…”

mentioning

confidence: 99%

Impact of the type of microcarrier and agitation modes on the expansion performances of mesenchymal stem cells derived from umbilical cord

Loubière

Sion

Isla

et al. 2019

Biotechnology Progress

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The present study proposed to compare the impact of agitation mode (static, orbital, and mechanical) on the culture of mesenchymal stem cells extracted from the Wharton's jelly of umbilical cords (WJ‐MSC), in a clinical grade culture medium, using human platelet lysate and different xeno‐free microcarriers. Attachment, expansion, and detachment performances were characterized by a new dedicated tool of microscopic image posttreatment, allowing an in situ cell counting without detachment step. Results showed that performances in static mode were not necessarily representative of those obtained in dynamic mode. Moreover, impacts on nutrient consumptions and metabolite productions were identified, such as a higher glutamine consumption when Cytodex‐1 microcarriers were used. The detachment strategy used was relatively efficient for Star‐Plus, Plastic‐Plus, and Hillex II, but not sufficient for Cytodex‐1. Despite Cytodex‐1 presented promising attachment and expansion performances, Star‐Plus and Plastic‐Plus showed a better compromise, respectively, for the orbital and the mechanical agitation modes.

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“…Further to this, stirred-suspension bioreactors are currently employed in biopharmaceutical production and therefore their design and operation are well-understood [5], with the potential to meet the expected manufacturing demands of large-scale BM-hMSC therapies [6]. The use of serum-free medium with microcarriers for the expansion of BM-hMSCs has previously been demonstrated for uncontrolled processes [7][8][9] and therefore represents a viable alternative for large-scale serum free manufacture of BM-hMSCs.…”

Section: Introductionmentioning

confidence: 99%

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

Heathman

Nienow

Rafiq

et al. 2019

Biochemical Engineering Journal

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Highlights Superior control in the bioreactor led to improved hMSC quality, consistency and yield  At 25% dissolved oxygen in serum-free media, there was a 500 % increase in the hMSC yield  Process control significantly reduced the variation in hMSC yield to < 15% AbstractHuman Mesenchymal Stem Cells (hMSCs) are advancing through clinical development with the first allogeneic adult hMSC therapy receiving approval in Europe. To enable successful large-scale manufacture of hMSC therapies, increased product consistency and yield, and a reduced batch-tobatch variation must be achieved. This paper addresses ways to reduce variation by controlling the processing conditions, in particular the dissolved oxygen concentration (dO2), and the culture medium.Bone marrow derived hMSCs were cultured in DASGIP DASbox bioreactors on Plastic P-102L microcarriers in FBS-containing and serum free (SFM) media at various dO2 values from 100% to 10%, experiencing the same dO2 value throughout the culture process. The superior control of pH and dO2 in the bioreactor led to improved performances compared to poorly controlled spinner flasks, particularly at reduced dO2 concentrations. At 25% dO2, there was a 300 % increase in the BM-hMSC yield in the bioreactor across the two donor BM-hMSCs in SFM compared to FBS-containing medium.Overall, the process yield increased by an average of around 500% for both donors under controlled conditions in SFM at 25% dO2 in the bioreactor compared to the poorly controlled expansion at atmospheric conditions in FBS-containing medium in spinner flasks. Process control significantly reduced the BM-hMSC variation in yield from 79.1% in FBS-containing medium in spinner flasks to < 15% in controlled SFM bioreactor culture.3 KeywordsProcess control, serum-free, human mesenchymal stem cell, microcarrier expansion, harvest, dissolved oxygen

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Serum-free media formulations are cell line–specific and require optimization for microcarrier culture

Cited by 45 publications

References 71 publications

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

Impact of the type of microcarrier and agitation modes on the expansion performances of mesenchymal stem cells derived from umbilical cord

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

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