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Learning Towards Maturation of Defined Feeder-free Pluripotency Culture Systems: Lessons from Conventional Feeder-based Systems

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Abstract

Pluripotent stem cells (PSCs) are widely recognized as one of the most promising types of stem cells for applications in regenerative medicine, tissue engineering, disease modeling, and drug screening. This is due to their unique ability to differentiate into cells from all three germ layers and their capacity for indefinite self-renewal. Initially, PSCs were cultured using animal feeder cells, but these systems presented several limitations, particularly in terms of Good Manufacturing Practices (GMP) regulations. As a result, feeder-free systems were introduced as a safer alternative. However, the precise mechanisms by which feeder cells support pluripotency are not fully understood. More importantly, it has been observed that some aspects of the need for feeder cells like the optimal density and cell type can vary depending on conditions such as the developmental stage of the PSCs, phases of the culture protocol, the method used in culture for induction of pluripotency, and intrinsic variability of PSCs. Thus, gaining a better understanding of the divergent roles and necessity of feeder cells in various conditions would lead to the development of condition-specific defined feeder-free systems that resolve the failure of current feeder-free systems in some conditions. Therefore, this review aims to explore considerable feeder-related issues that can lead to the development of condition-specific feeder-free systems.

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Abbreviations

PSC:

Pluripotent stem cell

ESC:

Embryonic stem cell

iPSC:

Induced pluripotent stem cell

SSC:

Spermatogonial stem cell

VSEL:

Very small embryonic-like stem cell

MAPC:

multipotent adult progenitor cell

pGSC:

Pluripotent germline stem cell

GMP:

Good manufacturing practices

FGF:

Fibroblast growth factor

TGF-β:

Transforming growth factor

GDNF:

Glial cell line-derived neurotrophic factor

EGF:

Epidermal growth factor

LIF:

Leukemia inhibitory factor

ECM:

Extracellular Matrix

KSR:

Knockout serum replacement

MET:

Mesenchymal to epithelial transition

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  1. Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technology, Tarbiat Modares University, Tehran, Iran

    Bardia Khandani

  2. Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran, 14115111, Iran

    Mansoureh Movahedin

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  1. Bardia Khandani
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Bardia Khandani suggested the concept, designed the outline, collected and analyzed the data and wrote the manuscript. Mansoureh Movahedin contributed to the study conception and revised the manuscript with her scientific inputs. All authors read and approved the final manuscript.

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Correspondence to Mansoureh Movahedin.

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Khandani, B., Movahedin, M. Learning Towards Maturation of Defined Feeder-free Pluripotency Culture Systems: Lessons from Conventional Feeder-based Systems. Stem Cell Rev and Rep 20, 484–494 (2024). https://doi.org/10.1007/s12015-023-10662-7

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