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Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro

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Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro. / Trakarnsanga, Kongtana; Wilson, Marieangela C.; Heesom, Kate J.; Andrienko, Tatyana N.; Srisawat, Chatchawan; Frayne, Jan.

In: Scientific Reports, Vol. 8, No. 1, 1983, 31.01.2018.

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@article{339337fb8f3b40448b992e376fd509d9,
title = "Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro",
abstract = "Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been explored. In this study, we show not only OP9 co-culture, but factors secreted by OP9 cells in isolation increase the proliferative potential of adult erythroid cells by delaying differentiation and hence maintaining self-renewing cells for an extended duration. The number of reticulocytes obtained was increased by approximately 3.5-fold, bringing it closer to that required for a therapeutic product. To identify the factors responsible, we analysed the OP9 cell secretome using comparative proteomics, identifying 18 candidate proteins. These data reveal the potential to increase erythroid cell numbers from in vitro culture systems without the need for genetic manipulation or co-culture.",
author = "Kongtana Trakarnsanga and Wilson, {Marieangela C.} and Heesom, {Kate J.} and Andrienko, {Tatyana N.} and Chatchawan Srisawat and Jan Frayne",
year = "2018",
month = "1",
day = "31",
doi = "10.1038/s41598-018-20491-1",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Springer Nature",
number = "1",

}

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TY - JOUR

T1 - Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro

AU - Trakarnsanga, Kongtana

AU - Wilson, Marieangela C.

AU - Heesom, Kate J.

AU - Andrienko, Tatyana N.

AU - Srisawat, Chatchawan

AU - Frayne, Jan

PY - 2018/1/31

Y1 - 2018/1/31

N2 - Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been explored. In this study, we show not only OP9 co-culture, but factors secreted by OP9 cells in isolation increase the proliferative potential of adult erythroid cells by delaying differentiation and hence maintaining self-renewing cells for an extended duration. The number of reticulocytes obtained was increased by approximately 3.5-fold, bringing it closer to that required for a therapeutic product. To identify the factors responsible, we analysed the OP9 cell secretome using comparative proteomics, identifying 18 candidate proteins. These data reveal the potential to increase erythroid cell numbers from in vitro culture systems without the need for genetic manipulation or co-culture.

AB - Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been explored. In this study, we show not only OP9 co-culture, but factors secreted by OP9 cells in isolation increase the proliferative potential of adult erythroid cells by delaying differentiation and hence maintaining self-renewing cells for an extended duration. The number of reticulocytes obtained was increased by approximately 3.5-fold, bringing it closer to that required for a therapeutic product. To identify the factors responsible, we analysed the OP9 cell secretome using comparative proteomics, identifying 18 candidate proteins. These data reveal the potential to increase erythroid cell numbers from in vitro culture systems without the need for genetic manipulation or co-culture.

UR - http://www.scopus.com/inward/record.url?scp=85041631646&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-20491-1

DO - 10.1038/s41598-018-20491-1

M3 - Article

C2 - 29386568

AN - SCOPUS:85041631646

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1983

ER -