Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells

Research output: Contribution to journalJournal articlepeer-review

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Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. / Korshunova, Irina; Rhein, Sina; García-González, Diego; Stölting, Ines; Pfisterer, Ulrich; Barta, Anna; Dmytriyeva, Oksana; Kirkeby, Agnete; Schwaninger, Markus; Khodosevich, Konstantin.

In: JCI insight, Vol. 5, No. 4, e126268, 2020, p. 1-19.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Korshunova, I, Rhein, S, García-González, D, Stölting, I, Pfisterer, U, Barta, A, Dmytriyeva, O, Kirkeby, A, Schwaninger, M & Khodosevich, K 2020, 'Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells', JCI insight, vol. 5, no. 4, e126268, pp. 1-19. https://doi.org/10.1172/jci.insight.126268

APA

Korshunova, I., Rhein, S., García-González, D., Stölting, I., Pfisterer, U., Barta, A., Dmytriyeva, O., Kirkeby, A., Schwaninger, M., & Khodosevich, K. (2020). Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. JCI insight, 5(4), 1-19. [e126268]. https://doi.org/10.1172/jci.insight.126268

Vancouver

Korshunova I, Rhein S, García-González D, Stölting I, Pfisterer U, Barta A et al. Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. JCI insight. 2020;5(4):1-19. e126268. https://doi.org/10.1172/jci.insight.126268

Author

Korshunova, Irina ; Rhein, Sina ; García-González, Diego ; Stölting, Ines ; Pfisterer, Ulrich ; Barta, Anna ; Dmytriyeva, Oksana ; Kirkeby, Agnete ; Schwaninger, Markus ; Khodosevich, Konstantin. / Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. In: JCI insight. 2020 ; Vol. 5, No. 4. pp. 1-19.

Bibtex

@article{5164308054734703b419cb84000cbf6b,
title = "Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells",
abstract = "Cell therapy raises high hopes for better treatment of brain disorders. However, the majority of transplanted cells often die soon after transplantation and those that survive initially continue to die in the subacute phase, diminishing the impact of transplantations. In this study, we genetically modified transplanted human neural stem cells (hNSCs), from two distant embryonic SCs lines (H9 and RC17) to express one of four prosurvival factors - Hif1a, Akt1, Bcl-2, or Bcl-xl - and studied how these modifications improve short- and long-term survival of transplanted hNSCs. All genetic modifications dramatically increased survival of the transplanted hNSCs. Importantly, three out of four modifications also enhanced the exit of hNSCs from the cell cycle, thus avoiding aberrant growth of the transplants. Bcl-xl expression provided the strongest protection of transplanted cells, reducing both immediate and delayed cell death, and stimulated hNSC differentiation towards neuronal and oligodendroglial lineages. By designing hNSCs with drug-controlled expression of Bcl-xl, we demonstrated that short-term expression of a prosurvival factor can ensure the long-term survival of transplanted cells. Importantly, transplantation of Bcl-xl expressing hNSCs into mice suffering from stroke improved behavioral outcome and recovery of motor activity in mice.",
author = "Irina Korshunova and Sina Rhein and Diego Garc{\'i}a-Gonz{\'a}lez and Ines St{\"o}lting and Ulrich Pfisterer and Anna Barta and Oksana Dmytriyeva and Agnete Kirkeby and Markus Schwaninger and Konstantin Khodosevich",
year = "2020",
doi = "10.1172/jci.insight.126268",
language = "English",
volume = "5",
pages = "1--19",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "4",

}

RIS

TY - JOUR

T1 - Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells

AU - Korshunova, Irina

AU - Rhein, Sina

AU - García-González, Diego

AU - Stölting, Ines

AU - Pfisterer, Ulrich

AU - Barta, Anna

AU - Dmytriyeva, Oksana

AU - Kirkeby, Agnete

AU - Schwaninger, Markus

AU - Khodosevich, Konstantin

PY - 2020

Y1 - 2020

N2 - Cell therapy raises high hopes for better treatment of brain disorders. However, the majority of transplanted cells often die soon after transplantation and those that survive initially continue to die in the subacute phase, diminishing the impact of transplantations. In this study, we genetically modified transplanted human neural stem cells (hNSCs), from two distant embryonic SCs lines (H9 and RC17) to express one of four prosurvival factors - Hif1a, Akt1, Bcl-2, or Bcl-xl - and studied how these modifications improve short- and long-term survival of transplanted hNSCs. All genetic modifications dramatically increased survival of the transplanted hNSCs. Importantly, three out of four modifications also enhanced the exit of hNSCs from the cell cycle, thus avoiding aberrant growth of the transplants. Bcl-xl expression provided the strongest protection of transplanted cells, reducing both immediate and delayed cell death, and stimulated hNSC differentiation towards neuronal and oligodendroglial lineages. By designing hNSCs with drug-controlled expression of Bcl-xl, we demonstrated that short-term expression of a prosurvival factor can ensure the long-term survival of transplanted cells. Importantly, transplantation of Bcl-xl expressing hNSCs into mice suffering from stroke improved behavioral outcome and recovery of motor activity in mice.

AB - Cell therapy raises high hopes for better treatment of brain disorders. However, the majority of transplanted cells often die soon after transplantation and those that survive initially continue to die in the subacute phase, diminishing the impact of transplantations. In this study, we genetically modified transplanted human neural stem cells (hNSCs), from two distant embryonic SCs lines (H9 and RC17) to express one of four prosurvival factors - Hif1a, Akt1, Bcl-2, or Bcl-xl - and studied how these modifications improve short- and long-term survival of transplanted hNSCs. All genetic modifications dramatically increased survival of the transplanted hNSCs. Importantly, three out of four modifications also enhanced the exit of hNSCs from the cell cycle, thus avoiding aberrant growth of the transplants. Bcl-xl expression provided the strongest protection of transplanted cells, reducing both immediate and delayed cell death, and stimulated hNSC differentiation towards neuronal and oligodendroglial lineages. By designing hNSCs with drug-controlled expression of Bcl-xl, we demonstrated that short-term expression of a prosurvival factor can ensure the long-term survival of transplanted cells. Importantly, transplantation of Bcl-xl expressing hNSCs into mice suffering from stroke improved behavioral outcome and recovery of motor activity in mice.

U2 - 10.1172/jci.insight.126268

DO - 10.1172/jci.insight.126268

M3 - Journal article

C2 - 31999645

VL - 5

SP - 1

EP - 19

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 4

M1 - e126268

ER -

ID: 235583780