Hi, the Blood brain barrier(BBB) makes it therapeutically challenging if not impossible to treat neurological disorders. Cells are huge compared to many of the small molecules that the BBB filters out. It is a challenge in such treatments.

Dear Diego S.Maranan

Your idea by instuition is logic,but you have to understand the complexity and perfection o the BBB,so that this ideas will be not easy to realize ore some completely imposible!!! Please takeonly some hours to see enormous amount of scientifico literature characterizing the BBB and additionally the big amount of papers trying to influence it!!!

I will recommned you two papers for the beginning:

1)Targeted Delivery of Neural Stem Cells to the Brain Using

MRI-Guided Focused Ultrasound to Disrupt the Blood-

Brain Barrier

Alison Burgess1*, Carlos A. Ayala-Grosso2,3, Milan Ganguly1, Jessica F. Jorda˜o1,2,4, Isabelle Aubert2,4.,

Kullervo Hynynen1,5.doi:10.1371/journal.pone.0027877

2)Fetal Microchimerism in the Maternal Mouse Brain: A Novel Population

of Fetal Progenitor or Stem Cells Able to Cross the Blood–Brain Barrier?

Xiao-Wei Tan,a,b Hong Liao,b,c Li Sun,b Masaru Okabe,d Zhi-Cheng Xiao,b,e Gavin S. Dawea.doi: 10.1634/stemcells.2004-0169

Sincerely yours!

Gustavo.

Thanks, Emmanuel, and thanks, Gustavo for those two articles, which I'm adding to the current list of articles I'm looking at:

• Aleynik, A., Gernavage, K. M., Mourad, Y. S., Sherman, L. S., Liu, K., Gubenko, Y. A., & Rameshwar, P. (2014). Stem cell delivery of therapies for brain disorders. Clinical and Translational Medicine, 3, 24. https://doi.org/10.1186/2001-1326-3-24
• Bai, L., Lennon, D. P., Caplan, A. I., DeChant, A., Hecker, J., Kranso, J., … Miller, R. H. (2012). Hepatocyte growth factor mediates MSCs stimulated functional recovery in animal models of MS. Nature Neuroscience, 15(6), 862–870. https://doi.org/10.1038/nn.3109
• Banerjee, S., Bentley, P., Hamady, M., Marley, S., Davis, J., Shlebak, A., … Chataway, J. (2014). Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke. STEM CELLS Translational Medicine, 3(11), 1322–1330. https://doi.org/10.5966/sctm.2013-0178
• Berkowitz, A. L., Miller, M. B., Mir, S. A., Cagney, D., Chavakula, V., Guleria, I., … Chi, J. H. (2016). Glioproliferative Lesion of the Spinal Cord as a Complication of “Stem-Cell Tourism.” New England Journal of Medicine, 375(2), 196–198. https://doi.org/10.1056/NEJMc1600188
• Bliss, S. A., Sinha, G., Sandiford, O. A., Williams, L. M., Engelberth, D. J., Guiro, K., … Bryan, M. (2016). Mesenchymal stem cell–derived exosomes stimulate cycling quiescence and early breast cancer dormancy in bone marrow. Cancer Research, 76(19), 5832–5844.
• Boltze, J., Lukomska, B., Jolkkonen, J., & consortium, M.-I. (2014). Mesenchymal stromal cells in stroke: improvement of motor recovery or functional compensation? Journal of Cerebral Blood Flow & Metabolism, 34(8), 1420–1421.
• Fernandes, A. R., & Chari, D. M. (2016). Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy. Journal of Controlled Release, 238, 289–299.
• Gross, G., & Häupl, T. (Eds.). (2013). Stem cell-dependent therapies: mesenchymal stem cells in chronic inflammatory disorders. Berlin: De Gruyter.
• Harris, V. K., Yan, Q. J., Vyshkina, T., Sahabi, S., Liu, X., & Sadiq, S. A. (2012). Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. Journal of the Neurological Sciences, 313(1–2), 167–177. https://doi.org/10.1016/j.jns.2011.08.036
• Hendricks, B. K., Cohen-Gadol, A. A., & Miller, J. C. (2015). Novel delivery methods bypassing the blood-brain and blood-tumor barriers. Neurosurgical Focus, 38(3), E10.
• Hess, D. C., Wechsler, L. R., Clark, W. M., Savitz, S. I., Ford, G. A., Chiu, D., … Mays, R. W. (2017). Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Neurology, 16(5), 360–368. https://doi.org/10.1016/S1474-4422(17)30046-7
• Kim, S. M., Jeong, C. H., Woo, J. S., Ryu, C. H., Lee, J.-H., & Jeun, S.-S. (2016). In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution. International Journal of Nanomedicine, 11, 13.
• Liu, L., Eckert, M. A., Riazifar, H., Kang, D.-K., Agalliu, D., & Zhao, W. (2013). From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier? Stem Cells International, 2013. https://doi.org/10.1155/2013/435093
• Mangraviti, A., Tzeng, S. Y., Gullotti, D., Kozielski, K. L., Kim, J. E., Seng, M., … Vescovi, A. (2016). Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival. Biomaterials, 100, 53–66.
• Marquez-Curtis, L. A., & Janowska-Wieczorek, A. (2013). Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis. BioMed Research International, 2013.
• Peterson, A., Bansal, A., Hofman, F., Chen, T. C., & Zada, G. (2014). A systematic review of inhaled intranasal therapy for central nervous system neoplasms: an emerging therapeutic option. Journal of Neuro-Oncology, 116(3), 437–446.
• Pollock, K., Dahlenburg, H., Nelson, H., Fink, K. D., Cary, W., Hendrix, K., … Gutierrez, J. (2016). Human mesenchymal stem cells genetically engineered to overexpress brain-derived neurotrophic factor improve outcomes in Huntington’s disease mouse models. Molecular Therapy, 24(5), 965–977.
• S Hersh, D., S Wadajkar, A., B Roberts, N., G Perez, J., P Connolly, N., Frenkel, V., … J Kim, A. (2016). Evolving drug delivery strategies to overcome the blood brain barrier. Current Pharmaceutical Design, 22(9), 1177–1193.
• Steinberg, G. K., Kondziolka, D., Wechsler, L. R., Lunsford, L. D., Coburn, M. L., Billigen, J. B., … Schwartz, N. E. (2016). Clinical Outcomes of Transplanted Modified Bone Marrow–Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study. Stroke, STROKEAHA.116.012995. https://doi.org/10.1161/STROKEAHA.116.012995
• Tandon, P. N., & Seth, P. (2016). Cell therapy for neurological disorders: The elusive goal. Neurology India, 64(4), 612.
• Turner, L., & Knoepfler, P. (2016). Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. Cell Stem Cell, 19(2), 154–157. https://doi.org/10.1016/j.stem.2016.06.007
• Wang, Q., Duan, F., Wang, M., Wang, X., Liu, P., & Ma, L. (2016). Effect of stem cell-based therapy for ischemic stroke treatment: A meta-analysis. Clinical Neurology and Neurosurgery, 146, 1–11.
• Webb, R. L., Kaiser, E. E., Scoville, S. L., Thompson, T. A., Fatima, S., Pandya, C., … Stice, S. L. (2017). Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model. Translational Stroke Research, 1–10. https://doi.org/10.1007/s12975-017-0599-2
• Young, J. S., Morshed, R. A., Kim, J. W., Balyasnikova, I. V., Ahmed, A. U., & Lesniak, M. S. (2014). Advances in stem cells, induced pluripotent stem cells, and engineered cells: delivery vehicles for anti-glioma therapy. Expert Opinion on Drug Delivery, 11(11), 1733–1746.

Diego S Maranan

Thankyou very much for your nice list,I will also look some of hte recommneded papers!!! thes is undoubtelly avery active topic!

Sincerely yours!

Gustavo

Any new finding about stem cells and the BBB???

Gustavo