The Systematic Production of Cells for Cell Therapies

Kirouac, Daniel C.; Zandstra, Peter W.

doi:10.1016/j.stem.2008.09.001

Cited by 277 publications

(212 citation statements)

References 128 publications

(125 reference statements)

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“…The comprehension and optimization of the expansion and differentiation process of HMSCs will contribute to maximi-zation of cell yield, reduction of cell culture and a decrease of total process costs ( Gong et al, 2009;Kirouac and Zandstra, 2008). In culture conditions, cells consume mostly glucose as substrate for the generation of cellular energy (ATP).…”

Section: Groupmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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Cellular systems implanted into an injured nerve may produce growth factors or extracellular matrix molecules, modulate the inflammatory process and eventually improve nerve regeneration. In the present study, we evaluated the therapeutic value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after axonotmesis injury associated to Vivosorbs membrane. During HMSCs expansion and differentiation in neuroglial-like cells, the culture medium was collected at 48, 72 and 96 h for nuclear magnetic resonance (NMR) analysis in order to evaluate the metabolic profile. To correlate the HMSCs ability to differentiate and survival capacity in the presence of the Vivosorbs membrane, the [Ca 2þ ]i of undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the epifluorescence technique using the Fura-2AM probe. The Vivosorbs membrane proved to be adequate and used as scaffold associated with undiffer-entiated HMSCs or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs or neuroglial differentiated HMSCs with or without the Vivosorbs membrane. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT), and withdrawal reflex latency (WRL).Stereological analysis was carried out on regenerated nerve fibers. In vitro investigation showed the formation of typical neuroglial cells after differentiation, which were positively stained for the typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN.NMR showed clear evidence that HMSCs expansion is glycolysis-dependent but their differentiation requires the switch of the metabolic profile to oxidative metabolism. In vivo studies showed enhanced recovery of motor and sensory function in animals treated with transplanted undifferentiated and differentiated HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC from the umbilical cord Wharton jelly might be useful for improving the clinical outcome after peripheral nerve lesion.

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Section: Groupmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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“…23 For tendon repair, previous studies in rodents showed that at least 10 6 BMSCs were required, 3,5,24 so it is not surprising that many more cells are needed in human patients. An optimized strategy for the in vitro expansion of stem cells while maintaining their undifferentiated stem cell characteristics is therefore essential.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Mediated Efficient Expansion of Human Tendon–Derived Stem CellsIn Vitro

Lee

Lui

Rui

2012

Tissue Engineering Part A

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Tendons regenerate and repair slowly and inefficiently after injury. Tendon-derived stem cells (TDSCs) have been isolated recently and have been shown to promote tendon repair. The ability to achieve sufficient numbers of cells for transplantation is essential for their clinical application. In this study, we aimed to study the effect of low oxygen (O 2 ) tension (2%) on the clonogenicity, metabolic rate, DNA incorporation, population doubling time, b-galactosidase activity, immunophenotypes, multilineage differentiation potential, and tenocyte-like properties of human TDSCs (hTDSCs). hTDSCs were isolated from patellar tendon and characterized according to their adherence to plastic; colony-forming ability; multilineage differentiation potential; and high expression level of CD44, CD73, CD 90, and CD105 but low CD34, CD45, CD146, and Stro-1 at 20% O 2 tension. Low O 2 tension increased DNA incorporation but not metabolic rate of hTDSCs. It increased cell number 25% and the number of colonies but reduced the osteogenic, adipogenic, and chondrogenic differentiation potential of hTDSCs. The reduction in differentiation potential was associated with lower messenger RNA (mRNA) expression ratios of some lineage-related markers, including BGLAP, ALP, C/EBPa, PPARc2, ACAN, and SOX9; the expression of a tendon-related marker, TNMD, was greater. There was no significant difference in the production of collagenous to noncollagenous protein ratio; the immunophenotypes and b-galactosidase activity were similar at 2% and 20% O 2 tension. Hypoxia-preconditioned hTDSCs could successfully differentiate at 20% O 2 tension, as shown by the return of the mRNA expression ratios of lineage-related markers to levels comparable to cells pre-incubated and differentiated at 20% O 2 tension. In conclusion, hypoxia is advantageous for efficient expansion of hTDSCs in vitro for tendon tissue engineering.

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“…Closed culture/expansion systems have been developed to exchange medium in large capacity tissue culture flasks using stopcocks and gravity-based flow to minimize the risk of operator error during the culture expansion process [4]. Bioreactors with controlled flow rates and built in monitors for cell viability, lactate production, pH/ pO 2 , and glucose levels need to be made efficient, practical, and scalable to current and future needs [7]. The use of automated, computer-controlled devices has the potential to reduce the risk of operator error during the culture period.…”

Section: Closed System Manufacturing Devicesmentioning

confidence: 99%

Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

et al. 2011

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Subcutaneous fat has emerged as an alternative tissue source for stromal/stem cells in regenerative medicine. Over the past decade, international research efforts have established a wealth of basic science and preclinical evidence regarding the differentiation potential and regenerative properties of both freshly processed, heterogeneous stromal vascular fraction cells and culture expanded, relatively homogeneous adipose-derived stromal/stem cells. The stage has been set for clinicians to translate adipose-derived cells from the bench to the bedside; however, this process will involve “development” steps that fall outside of traditional “hypothesis-driven, mechanism-based” paradigm. This concise review examines the next stages of the development process for therapeutic applications of adipose-derived cells and highlights the current state of the art regarding clinical trials. It is recommended that the experiments addressing these issues be reported comprehensively in the peer-review literature. This transparency will accelerate the standardization and reproducibility of adipose-derived cell therapies with respect to their efficacy and safety.

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The Systematic Production of Cells for Cell Therapies

Cited by 277 publications

References 128 publications

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Hypoxia-Mediated Efficient Expansion of Human Tendon–Derived Stem CellsIn Vitro

Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

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