Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease

Shawna E. Wicks; Heaven Londot; Bo Zhang; Jennifer Dowden; Jessica Klopf-Eiermann; Jeanne M. Fisher-Perkins; Cynthia B. Trygg; Brittni A. Scruggs; Xiujuan Zhang; Jeffrey M. Gimble; Bruce A. Bunnell; Paul J. Pistell

doi:10.1016/j.bbr.2011.07.051

Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease

Shawna E. Wicks, Heaven Londot, Bo Zhang, Jennifer Dowden, Jessica Klopf-Eiermann, Jeanne M. Fisher-Perkins, Cynthia B. Trygg, Brittni A. Scruggs, Xiujuan Zhang, Jeffrey M. Gimble, Bruce A. Bunnell, Paul J. Pistell

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.

Original language	English
Pages (from-to)	415-425
Number of pages	11
Journal	Behavioural Brain Research
Volume	225
Issue number	2
DOIs	https://doi.org/10.1016/j.bbr.2011.07.051
State	Published - 1 Dec 2011

Keywords

Adipose-derived stem/stromal cells
Gait analysis
Krabbe disease
Mesenchymal stem/stromal cells
Motor function
Twitcher mice

Access to Document

10.1016/j.bbr.2011.07.051

Cite this

Wicks, S. E., Londot, H., Zhang, B., Dowden, J., Klopf-Eiermann, J., Fisher-Perkins, J. M., Trygg, C. B., Scruggs, B. A., Zhang, X., Gimble, J. M., Bunnell, B. A., & Pistell, P. J. (2011). Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease. Behavioural Brain Research, 225(2), 415-425. https://doi.org/10.1016/j.bbr.2011.07.051

@article{69126f481e96499daddc6411f32fb0ae,

title = "Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease",

abstract = "One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.",

keywords = "Adipose-derived stem/stromal cells, Gait analysis, Krabbe disease, Mesenchymal stem/stromal cells, Motor function, Twitcher mice",

author = "Wicks, {Shawna E.} and Heaven Londot and Bo Zhang and Jennifer Dowden and Jessica Klopf-Eiermann and Fisher-Perkins, {Jeanne M.} and Trygg, {Cynthia B.} and Scruggs, {Brittni A.} and Xiujuan Zhang and Gimble, {Jeffrey M.} and Bunnell, {Bruce A.} and Pistell, {Paul J.}",

note = "Funding Information: J.M.G., P.J.P., S.E.W., and B.A.B. were supported by grant 1 R21 NS059665 to B.A.B. This work used Animal Metabolism and Behavior Core facilities supported by a NORC Center Grant # 1P30 DK072476 entitled “Nutritional Programming: Environmental and Molecular Interactions” sponsored by NIDDK. Funding entities did not contribute to study design, data analysis, manuscript writing or publication decisions. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

year = "2011",

month = dec,

day = "1",

doi = "10.1016/j.bbr.2011.07.051",

language = "English",

volume = "225",

pages = "415--425",

journal = "Behavioural Brain Research",

issn = "0166-4328",

publisher = "Elsevier",

number = "2",

}

Wicks, SE, Londot, H, Zhang, B, Dowden, J, Klopf-Eiermann, J, Fisher-Perkins, JM, Trygg, CB, Scruggs, BA, Zhang, X, Gimble, JM, Bunnell, BA & Pistell, PJ 2011, 'Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease', Behavioural Brain Research, vol. 225, no. 2, pp. 415-425. https://doi.org/10.1016/j.bbr.2011.07.051

TY - JOUR

T1 - Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease

AU - Wicks, Shawna E.

AU - Londot, Heaven

AU - Zhang, Bo

AU - Dowden, Jennifer

AU - Klopf-Eiermann, Jessica

AU - Fisher-Perkins, Jeanne M.

AU - Trygg, Cynthia B.

AU - Scruggs, Brittni A.

AU - Zhang, Xiujuan

AU - Gimble, Jeffrey M.

AU - Bunnell, Bruce A.

AU - Pistell, Paul J.

N1 - Funding Information: J.M.G., P.J.P., S.E.W., and B.A.B. were supported by grant 1 R21 NS059665 to B.A.B. This work used Animal Metabolism and Behavior Core facilities supported by a NORC Center Grant # 1P30 DK072476 entitled “Nutritional Programming: Environmental and Molecular Interactions” sponsored by NIDDK. Funding entities did not contribute to study design, data analysis, manuscript writing or publication decisions. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.

AB - One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.

KW - Adipose-derived stem/stromal cells

KW - Gait analysis

KW - Krabbe disease

KW - Mesenchymal stem/stromal cells

KW - Motor function

KW - Twitcher mice

UR - http://www.scopus.com/inward/record.url?scp=80052968312&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2011.07.051

DO - 10.1016/j.bbr.2011.07.051

M3 - Article

C2 - 21840342

AN - SCOPUS:80052968312

SN - 0166-4328

VL - 225

SP - 415

EP - 425

JO - Behavioural Brain Research

JF - Behavioural Brain Research

IS - 2

ER -

Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this