Skip to main content
SpringerLink
Log in

Application of Muse Cell Therapy to Stroke

  • Chapter
  • First Online:
Muse Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1103))

Abstract

Stroke is defined as a sudden onset of neurologic deficits arising from cerebrovascular complications. It is the second common cause of death around the world and the major cause of disability. Because brain is an organ with complicated neural networks and neurons are highly differentiated, it has been traditionally considered to possess a limited potential for regeneration. The number of stroke patients is increasing, and stroke represents a serious problem from the viewpoint of the national medical economy. Even with the current sophisticated treatments, more than half of stroke patient survivors remain disabled. Therefore, it is imperative to develop a new treatment for promoting functional recovery and repair of the lost neurological circuit. Multilineage-differentiating stress-enduring (Muse) cells are endogenous non-tumorigenic stem cells with pluripotency. After transplantation, Muse cells recognize the injured site through their specific receptor for damage signal, home preferentially into these tissues and spontaneously differentiate into tissue-compatible cells to replace the lost cells, and repair the tissue, delivering functional and structural regeneration. These properties are desirable for the treatment of strokes and advantageous compared to other stem cell therapies. Here, we describe the current status of stem cell therapies for stroke and future possibilities of Muse cell therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B (2008) Neocortical glial cell numbers in human brains. Neurobiol Aging 29:1754–1762

    Article  CAS  Google Scholar 

  2. Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 98:4710–4715

    Article  CAS  Google Scholar 

  3. Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, Shen J, Mao Y, Banwait S, Greenberg DA (2006) Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA 103:13198–13202

    Article  CAS  Google Scholar 

  4. Tatebayashi K, Tanaka Y, Nakano-Doi A, Sakuma R, Kamachi S, Shirakawa M, Uchida K, Kageyama H, Takagi T, Yoshimura S, Matsuyama T, Nakagomi T (2017) Identification of multipotent stem cells in human brain tissue following stroke. Stem Cells Dev 26:787–797

    Article  CAS  Google Scholar 

  5. Takata M, Nakagomi T, Kashiwamura S, Nakano-Doi A, Saino O, Nakagomi N, Okamura H, Mimura O, Taguchi A, Matsuyama T (2012) Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke. Cell Death Differ 19:756–767

    Article  CAS  Google Scholar 

  6. Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612–1623

    Article  CAS  Google Scholar 

  7. Khalili MA, Sadeghian-Nodoushan F, Fesahat F, Mir-Esmaeili SM, Anvari M, Hekmati-Moghadam SH (2014) Mesenchymal stem cells improved the ultrastructural morphology of cerebral tissues after subarachnoid hemorrhage in rats. Exp Neurobiol 23:77–85

    Article  Google Scholar 

  8. Stonesifer C, Corey S, Ghanekar S, Diamandis Z, Acosta SA, Borlongan CV (2017) Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms. Prog Neurobiol 158:94–131

    Article  CAS  Google Scholar 

  9. Kondziolka D, Steinberg GK, Wechsler L, Meltzer CC, Elder E, Gebel J, Decesare S, Jovin T, Zafonte R, Lebowitz J, Flickinger JC, Tong D, Marks MP, Jamieson C, Luu D, Bell-Stephens T, Teraoka J (2005) Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 103:38–45

    Article  Google Scholar 

  10. Savitz SI, Dinsmore J, Wu J, Henderson GV, Stieg P, Caplan LR (2005) Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study. Cerebrovasc Dis 20:101–107

    Article  Google Scholar 

  11. Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882

    Article  Google Scholar 

  12. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY (2010) A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28:1099–1106

    Article  Google Scholar 

  13. Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD (2011) Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain 134:1790–1807

    Article  Google Scholar 

  14. Bhasin A, Srivastava MV, Kumaran SS, Mohanty S, Bhatia R, Bose S, Gaikwad S, Garg A, Airan B (2011) Autologous mesenchymal stem cells in chronic stroke. Cerebrovasc Dis Extra 1:93–104

    Article  Google Scholar 

  15. Diez-Tejedor E, Gutierrez-Fernandez M, Martinez-Sanchez P, Rodriguez-Frutos B, Ruiz-Ares G, Lara ML, Gimeno BF (2014) Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. J Stroke Cerebrovasc Dis 23:2694–2700

    Article  Google Scholar 

  16. Steinberg GK, Kondziolka D, Wechsler LR, Lunsford LD, Coburn ML, Billigen JB, Kim AS, Johnson JN, Bates D, King B, Case C, McGrogan M, Yankee EW, Schwartz NE (2016) Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a phase 1/2a study. Stroke 47:1817–1824

    Article  Google Scholar 

  17. Barbosa Da Fonseca LM, Battistella V, de Freitas GR, Gutfilen B, Dos Santos Goldenberg RC, Maiolino A, Wajnberg E, Rosado De Castro PH, Mendez-Otero R, Andre C (2009) Early tissue distribution of bone marrow mononuclear cells after intra-arterial delivery in a patient with chronic stroke. Circulation 120:539–541

    Article  Google Scholar 

  18. Suarez-Monteagudo C, Hernandez-Ramirez P, Alvarez-Gonzalez L, Garcia-Maeso I, de la Cuetara-Bernal K, Castillo-Diaz L, Bringas-Vega ML, Martinez-Aching G, Morales-Chacon LM, Baez-Martin MM, Sanchez-Catasus C, Carballo-Barreda M, Rodriguez-Rojas R, Gomez-Fernandez L, Alberti-Amador E, Macias-Abraham C, Balea ED, Rosales LC, Del Valle Perez L, Ferrer BB, Gonzalez RM, Bergado JA (2009) Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study. Restor Neurol Neurosci 27:151–161

    PubMed  Google Scholar 

  19. Savitz SI, Misra V, Kasam M, Juneja H, Cox CS Jr, Alderman S, Aisiku I, Kar S, Gee A, Grotta JC (2011) Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol 70:59–69

    Article  Google Scholar 

  20. Battistella V, de Freitas GR, da Fonseca LM, Mercante D, Gutfilen B, Goldenberg RC, Dias JV, Kasai-Brunswick TH, Wajnberg E, Rosado-De-Castro PH, Alves-Leon SV, Mendez-Otero R, Andre C (2011) Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen Med 6:45–52

    Article  CAS  Google Scholar 

  21. Moniche F, Gonzalez A, Gonzalez-Marcos JR, Carmona M, Pinero P, Espigado I, Garcia-Solis D, Cayuela A, Montaner J, Boada C, Rosell A, Jimenez MD, Mayol A, Gil-Peralta A (2012) Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke 43:2242–2244

    Article  Google Scholar 

  22. Friedrich MA, Martins MP, Araujo MD, Klamt C, Vedolin L, Garicochea B, Raupp EF, Sartori El Ammar J, Machado DC, Costa JC, Nogueira RG, Rosado-De-Castro PH, Mendez-Otero R, Freitas GR (2012) Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant 21(Suppl 1):S13–S21

    Article  Google Scholar 

  23. Rosado-De-Castro PH, Schmidt Fda R, Battistella V, Lopes De Souza SA, Gutfilen B, Goldenberg RC, Kasai-Brunswick TH, Vairo L, Silva RM, Wajnberg E, Alvarenga Americano Do Brasil PE, Gasparetto EL, Maiolino A, Alves-Leon SV, Andre C, Mendez-Otero R, Rodriguez De Freitas G, Barbosa Da Fonseca LM (2013) Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regen Med 8:145–155

    Article  CAS  Google Scholar 

  24. Taguchi A, Sakai C, Soma T, Kasahara Y, Stern DM, Kajimoto K, Ihara M, Daimon T, Yamahara K, Doi K, Kohara N, Nishimura H, Matsuyama T, Naritomi H, Sakai N, Nagatsuka K (2015) Intravenous autologous bone marrow mononuclear cell transplantation for stroke: phase1/2a clinical trial in a homogeneous group of stroke patients. Stem Cells Dev 24:2207–2218

    Article  CAS  Google Scholar 

  25. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M, Waldman D, Leider-Trejo L, Toren A, Constantini S, Rechavi G (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6:e1000029

    Article  Google Scholar 

  26. Osanai T, Houkin K, Uchiyama S, Minematsu K, Taguchi A, Terasaka S (2017) Treatment evaluation of acute stroke for using in regenerative cell elements (TREASURE) trial: rationale and design. Int J Stroke 1747493017743057

    Google Scholar 

  27. Uchida N, Kushida Y, Kitada M, Wakao S, Kumagai N, Kuroda Y, Kondo Y, Hirohara Y, Kure S, Chazenbalk G, Dezawa M (2017) Beneficial effects of systemically administered human Muse cells in Adriamycin nephropathy. J Am Soc Nephrol 28:2946–2960

    Article  CAS  Google Scholar 

  28. Uchida H, Sakata H, Fujimura M, Niizuma K, Kushida Y, Dezawa M, Tominaga T (2015) Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities. Brain Res 1629:318–328

    Article  CAS  Google Scholar 

  29. Uchida H, Morita T, Niizuma K, Kushida Y, Kuroda Y, Wakao S, Sakata H, Matsuzaka Y, Mushiake H, Tominaga T, Borlongan CV, Dezawa M (2016) Transplantation of unique subpopulation of fibroblasts, Muse cells, ameliorates experimental stroke possibly via robust neuronal differentiation. Stem Cells 34:160–173

    Article  CAS  Google Scholar 

  30. Uchida H, Niizuma K, Kushida Y, Wakao S, Tominaga T, Borlongan CV, Dezawa M (2017) Human Muse cells reconstruct neuronal circuitry in subacute lacunar stroke model. Stroke 48:428–435

    Article  Google Scholar 

  31. Yasuhara T, Matsukawa N, Hara K, Maki M, Ali MM, Yu SJ, Bae E, Yu G, Xu L, McGrogan M, Bankiewicz K, Case C, Borlongan CV (2009) Notch-induced rat and human bone marrow stromal cell grafts reduce ischemic cell loss and ameliorate behavioral deficits in chronic stroke animals. Stem Cells Dev 18:1501–1514

    Article  CAS  Google Scholar 

  32. Shen LH, Li Y, Chen J, Zacharek A, Gao Q, Kapke A, Lu M, Raginski K, Vanguri P, Smith A, Chopp M (2007) Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. J Cereb Blood Flow Metab 27:6–13

    Article  Google Scholar 

  33. Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M (2003) Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 92:692–699

    Article  CAS  Google Scholar 

  34. Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011

    Article  CAS  Google Scholar 

  35. Pappenheimer AM Jr, Harper AA, Moynihan M, Brockes JP (1982) Diphtheria toxin and related proteins: effect of route of injection on toxicity and the determination of cytotoxicity for various cultured cells. J Infect Dis 145:94–102

    Article  CAS  Google Scholar 

  36. Cummings BJ, Uchida N, Tamaki SJ, Salazar DL, Hooshmand M, Summers R, Gage FH, Anderson AJ (2005) Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci USA 102:14069–14074

    Article  CAS  Google Scholar 

  37. Yamauchi T, Kuroda Y, Morita T, Shichinohe H, Houkin K, Dezawa M, Kuroda S (2015) Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice. PLoS One 10:e0116009

    Article  Google Scholar 

  38. Li ZM, Zhang ZT, Guo CJ, Geng FY, Qiang F, Wang LX (2013) Autologous bone marrow mononuclear cell implantation for intracerebral hemorrhage-a prospective clinical observation. Clin Neurol Neurosurg 115:72–76

    Article  Google Scholar 

  39. Sharma A, Sane H, Gokulchandran N, Khopkar D, Paranjape A, Sundaram J, Gandhi S, Badhe P (2014) Autologous bone marrow mononuclear cells intrathecal transplantation in chronic stroke. Stroke Res Treat 2014:234095

    PubMed  PubMed Central  Google Scholar 

  40. Zhu J, Xiao Y, Li Z, Han F, Xiao T, Zhang Z, Geng F (2015) Efficacy of surgery combined with autologous bone marrow stromal cell transplantation for treatment of intracerebral hemorrhage. Stem Cells Int 2015:318269

    PubMed  PubMed Central  Google Scholar 

  41. Shimamura N, Kakuta K, Wang L, Naraoka M, Uchida H, Wakao S, Dezawa M, Ohkuma H (2017) Neuro-regeneration therapy using human Muse cells is highly effective in a mouse intracerebral hemorrhage model. Exp Brain Res 235:565–572

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan

    Kuniyasu Niizuma

  2. Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan

    Kuniyasu Niizuma

  3. Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan

    Kuniyasu Niizuma & Teiji Tominaga

  4. Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL, USA

    Cesar V. Borlongan

Authors
  1. Kuniyasu Niizuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cesar V. Borlongan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teiji Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kuniyasu Niizuma .

Editor information

Editors and Affiliations

  1. Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Mari Dezawa

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Japan KK, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Niizuma, K., Borlongan, C.V., Tominaga, T. (2018). Application of Muse Cell Therapy to Stroke. In: Dezawa, M. (eds) Muse Cells. Advances in Experimental Medicine and Biology, vol 1103. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56847-6_9

Download citation

Publish with us

Policies and ethics

Search

Navigation