Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

Hemmer K, Zhang M, van Wuellen T, Sakalem M, Tapia N, Baumuratov A, Kaltschmidt C, Kaltschmidt B, Schoeler HR, Zhang W, Schwamborn JC (2014)
Stem Cell Reports 3(3): 423-431.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ; ; ; ; ;
Abstract
Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.
Publishing Year
ISSN
PUB-ID

Cite this

Hemmer K, Zhang M, van Wuellen T, et al. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain. Stem Cell Reports. 2014;3(3):423-431.
Hemmer, K., Zhang, M., van Wuellen, T., Sakalem, M., Tapia, N., Baumuratov, A., Kaltschmidt, C., et al. (2014). Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain. Stem Cell Reports, 3(3), 423-431.
Hemmer, K., Zhang, M., van Wuellen, T., Sakalem, M., Tapia, N., Baumuratov, A., Kaltschmidt, C., Kaltschmidt, B., Schoeler, H. R., Zhang, W., et al. (2014). Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain. Stem Cell Reports 3, 423-431.
Hemmer, K., et al., 2014. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain. Stem Cell Reports, 3(3), p 423-431.
K. Hemmer, et al., “Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain”, Stem Cell Reports, vol. 3, 2014, pp. 423-431.
Hemmer, K., Zhang, M., van Wuellen, T., Sakalem, M., Tapia, N., Baumuratov, A., Kaltschmidt, C., Kaltschmidt, B., Schoeler, H.R., Zhang, W., Schwamborn, J.C.: Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain. Stem Cell Reports. 3, 423-431 (2014).
Hemmer, Kathrin, Zhang, Mingyue, van Wuellen, Thea, Sakalem, Marna, Tapia, Natalia, Baumuratov, Aidos, Kaltschmidt, Christian, Kaltschmidt, Barbara, Schoeler, Hans R., Zhang, Weiqi, and Schwamborn, Jens C. “Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain”. Stem Cell Reports 3.3 (2014): 423-431.
This data publication is cited in the following publications:
This publication cites the following data publications:

9 Citations in Europe PMC

Data provided by Europe PubMed Central.

Generation of diverse neural cell types through direct conversion.
Petersen GF, Strappe PM., World J Stem Cells 8(2), 2016
PMID: 26981169
SOX2 and SOX2-MYC Reprogramming Process of Fibroblasts to the Neural Stem Cells Compromised by Senescence.
Winiecka-Klimek M, Smolarz M, Walczak MP, Zieba J, Hulas-Bigoszewska K, Kmieciak B, Piaskowski S, Rieske P, Grzela DP, Stoczynska-Fidelus E., PLoS ONE 10(11), 2015
PMID: 26535892
Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts.
Kim J, Kim KP, Lim KT, Lee SC, Yoon J, Song G, Hwang SI, Scholer HR, Cantz T, Han DW., Sci Rep 5(), 2015
PMID: 26503743
Connectivity and circuitry in a dish versus in a brain.
Chinchalongporn V, Koppensteiner P, Pre D, Thangnipon W, Bilo L, Arancio O., Alzheimers Res Ther 7(1), 2015
PMID: 26045718
Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture.
Moreno EL, Hachi S, Hemmer K, Trietsch SJ, Baumuratov AS, Hankemeier T, Vulto P, Schwamborn JC, Fleming RM., Lab Chip 15(11), 2015
PMID: 25902196
Advances in reprogramming-based study of neurologic disorders.
Nityanandam A, Baldwin KK., Stem Cells Dev. 24(11), 2015
PMID: 25749371

16 References

Data provided by Europe PubMed Central.

Direct reprogramming of human astrocytes into neural stem cells and neurons.
Corti S, Nizzardo M, Simone C, Falcone M, Donadoni C, Salani S, Rizzo F, Nardini M, Riboldi G, Magri F, Zanetta C, Faravelli I, Bresolin N, Comi GP., Exp. Cell Res. 318(13), 2012
PMID: 22426197
Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.
Davies SJ, Shih CH, Noble M, Mayer-Proschel M, Davies JE, Proschel C., PLoS ONE 6(3), 2011
PMID: 21407803
Mammalian neural stem cells.
Gage FH., Science 287(5457), 2000
PMID: 10688783
Glia: initiators and progressors of pathology in Parkinson's disease.
Halliday GM, Stevens CH., Mov. Disord. 26(1), 2011
PMID: 21322014
Direct reprogramming of fibroblasts into neural stem cells by defined factors.
Han DW, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo MJ, Zaehres H, Wu G, Frank S, Moritz S, Greber B, Yang JH, Lee HT, Schwamborn JC, Storch A, Scholer HR., Cell Stem Cell 10(4), 2012
PMID: 22445517
Direct reprogramming of mouse fibroblasts to neural progenitors.
Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S., Proc. Natl. Acad. Sci. U.S.A. 108(19), 2011
PMID: 21521790
Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells.
Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M., Proc. Natl. Acad. Sci. U.S.A. 109(7), 2012
PMID: 22308465
Induction of human neuronal cells by defined transcription factors.
Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M., Nature 476(7359), 2011
PMID: 21617644
Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.
Ring KL, Tong LM, Balestra ME, Javier R, Andrews-Zwilling Y, Li G, Walker D, Zhang WR, Kreitzer AC, Huang Y., Cell Stem Cell 11(1), 2012
PMID: 22683203
Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors.
Sheng C, Zheng Q, Wu J, Xu Z, Wang L, Li W, Zhang H, Zhao XY, Liu L, Wang Z, Guo C, Wu HJ, Liu Z, Wang L, He S, Wang XJ, Chen Z, Zhou Q., Cell Res. 22(1), 2012
PMID: 22064700
Generation of functional neurons and glia from multipotent adult mouse germ-line stem cells
Streckfuss-Bömeke K., Vlasov A., Hülsmann S., Yin D., Nayernia K., Engel W., Hasenfuss G., Guan K.., 2009
Direct conversion of fibroblasts into stably expandable neural stem cells.
Thier M, Worsdorfer P, Lakes YB, Gorris R, Herms S, Opitz T, Seiferling D, Quandel T, Hoffmann P, Nothen MM, Brustle O, Edenhofer F., Cell Stem Cell 10(4), 2012
PMID: 22445518
Direct conversion of fibroblasts to functional neurons by defined factors.
Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M., Nature 463(7284), 2010
PMID: 20107439
A fresh look at iPS cells.
Yamanaka S., Cell 137(1), 2009
PMID: 19345179
Mechanisms and functional implications of adult neurogenesis.
Zhao C, Deng W, Gage FH., Cell 132(4), 2008
PMID: 18295581

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 25241741
PubMed | Europe PMC

Search this title in

Google Scholar