Pdf

Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin.

Molecular and cellular neurosciences | March 15, 2012 |

Olson, Scott D | Kambal, Amal | Pollock, Kari | Mitchell, Gaela-Marie | Stewart, Heather | Kalomoiris, Stefanos | Cary, Whitney | Nacey, Catherine | Pepper, Karen | Nolta, Jan A
Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Abstract

Huntington's disease (HD) is a fatal, autosomal dominant neurodegenerative disorder caused by an expanded trinucleotide (CAG) repeat in exon 1 of the h ... ensitometry. These results are encouraging for expanding the therapeutic abilities of both RNAi and MSC for future treatments of Huntington's disease.

Huntington's disease (HD) is a fatal, autosomal dominant neurodegenerative disorder caused by an expanded trinucleotide (CAG) repeat in exon 1 of the huntingtin gene (Htt). This expansion creates a toxic polyglutamine tract in the huntingtin protein (HTT). Currently, there is no treatment for either the progression or prevention of the disease. RNA interference (RNAi) technology has shown promise in transgenic mouse models of HD by reducing expression of mutant HTT and slowing disease progression. The advancement of RNAi therapies to human clinical trials is hampered by problems delivering RNAi to affected neurons in a robust and sustainable manner. Mesenchymal stem cells (MSC) have demonstrated a strong safety profile in both completed and numerous ongoing clinical trials. MSC exhibit a number of innate therapeutic effects, such as immune system modulation, homing to injury, and cytokine release into damaged microenvironments. The ability of MSC to transfer larger molecules and even organelles suggested their potential usefulness as delivery vehicles for therapeutic RNA inhibition. In a series of model systems we have found evidence that MSC can transfer RNAi targeting both reporter genes and mutant huntingtin in neural cell lines. MSC expressing shRNA antisense to GFP were found to decrease expression of GFP in SH-SY5Y cells after co-culture when assayed by flow cytometry. Additionally MSC expressing shRNA antisense to HTT were able to decrease levels of mutant HTT expressed in both U87 and SH-SY5Y target cells when assayed by Western blot and densitometry. These results are encouraging for expanding the therapeutic abilities of both RNAi and MSC for future treatments of Huntington's disease.

High Discussion
Low Discussion
Paper
Fig 1
Fig 2
Fig 3
Fig 4
Fig 5
Fig 6
Fig 7

Summary of The Overall Paper

Click to enter summary

Sign up to leave a summary.


Sign up to leave a summary.



Comments
Nihms512919f1
Fig 1. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f1
Fig 1. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 1

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f2
Fig 2. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f2
Fig 2. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 2

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f3
Fig 3. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f3
Fig 3. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 3

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f4
Fig 4. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f4
Fig 4. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 4

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f5
Fig 5. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f5
Fig 5. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 5

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f6
Fig 6. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f6
Fig 6. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 6

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments
Nihms512919f7
Fig 7. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.
Nihms512919f7
Fig 7. Olson, Kambal, et al. "Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin." Molecular and cellular neurosciences 49.3 (2012): 271-81. Web.

Fig 7

Click to enter summary

Sign up to leave a summary.


Click to list methods

Sign up to leave a summary.



Comments