Stereotactic Brain Injection of Human Umbilical Cord Blood Mesenchymal Stem Cells in Patients with Alzheimer's Disease Dementia: A Phase 1 Clinical Trial

Overview

Journal Alzheimers Dement (N Y)

Date 2018 Jun 2

PMID 29854930

Citations 86

Authors

Hee Jin Kim

Sang Won Seo

Jong Wook Chang

Jung Il Lee

Chi Hun Kim

Juhee Chin

Soo Jin Choi

Hunki Kwon

Hyuk Jin Yun

Jong Min Lee

Sung Tae Kim

Yearn Seong Choe

Kyung-Han Lee

Duk L Na

Affiliations

Soon will be listed here.

Abstract

Introduction: We conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer's disease to evaluate the safety and dose-limiting toxicity of stereotactic brain injection of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs).

Methods: The low- (n = 3) and high-dose (n = 6) groups received a total of 3.0 × 10 cells/60 μL and 6.0 × 10 cells/60 μL, respectively, into the bilateral hippocampi and right precuneus.

Results: No patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n = 9), followed by headache (n = 4), dizziness (n = 3), and postoperative delirium (n = 3). There was no dose-limiting toxicity.

Discussion: Administration of hUCB-MSCs into the hippocampus and precuneus by stereotactic injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy.

Clinical Trial Registration: ClinicalTrial.gov identifier NCT01297218 and NCT01696591.

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References

Caplan A . Mesenchymal stem cells. J Orthop Res. 1991; 9(5):641-50. DOI: 10.1002/jor.1100090504. View

Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K . Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006; 112(4):389-404. PMC: 3906709. DOI: 10.1007/s00401-006-0127-z. View

Venkataramana N, Kumar S, Balaraju S, Radhakrishnan R, Bansal A, Dixit A . Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Transl Res. 2010; 155(2):62-70. DOI: 10.1016/j.trsl.2009.07.006. View

Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W . Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series. J Am Geriatr Soc. 1999; 47(5):564-9. DOI: 10.1111/j.1532-5415.1999.tb02571.x. View

Rafii M, Baumann T, Bakay R, Ostrove J, Siffert J, Fleisher A . A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease. Alzheimers Dement. 2014; 10(5):571-81. DOI: 10.1016/j.jalz.2013.09.004. View

Lee O, Kuo T, Chen W, Lee K, Hsieh S, Chen T . Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2003; 103(5):1669-75. DOI: 10.1182/blood-2003-05-1670. View

Kim J, Kim D, Kim J, Lee D, Jeon H, Kwon S . Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-β plaques. Cell Death Differ. 2011; 19(4):680-91. PMC: 3307982. DOI: 10.1038/cdd.2011.140. View

Mintun M, Larossa G, Sheline Y, Dence C, Lee S, Mach R . [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006; 67(3):446-52. DOI: 10.1212/01.wnl.0000228230.26044.a4. View

Lee H, Lee J, Lee H, Shin J, Carter J, Sakamoto T . The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease. Neurosci Lett. 2010; 481(1):30-5. DOI: 10.1016/j.neulet.2010.06.045. View

10.

Cavanna A, Trimble M . The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006; 129(Pt 3):564-83. DOI: 10.1093/brain/awl004. View

11.

Kim J, Kim D, Kim D, Kim J, Jeong S, Jeon H . Galectin-3 secreted by human umbilical cord blood-derived mesenchymal stem cells reduces amyloid-beta42 neurotoxicity in vitro. FEBS Lett. 2010; 584(16):3601-8. DOI: 10.1016/j.febslet.2010.07.028. View

12.

Echavarri C, Burgmans S, Caballero M, Garcia-Bragado F, Verhey F, Uylings H . Co-occurrence of different pathologies in dementia: implications for dementia diagnosis. J Alzheimers Dis. 2012; 30(4):909-17. DOI: 10.3233/JAD-2012-111400. View

13.

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

14.

Ikonomovic M, Klunk W, Abrahamson E, Mathis C, Price J, Tsopelas N . Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008; 131(Pt 6):1630-45. PMC: 2408940. DOI: 10.1093/brain/awn016. View

15.

Kim H, Kim H, Oh K, Oh S, Koh S, Baik W . Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study. Stem Cells. 2014; 32(10):2724-31. DOI: 10.1002/stem.1770. View

16.

Lee M, Jang I, Yoo K, Sung K, Koo H . Stem and progenitor cells in human umbilical cord blood. Int J Hematol. 2010; 92(1):45-51. DOI: 10.1007/s12185-010-0619-4. View

17.

Karas G, Scheltens P, Rombouts S, Van Schijndel R, Klein M, Jones B . Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study. Neuroradiology. 2007; 49(12):967-76. DOI: 10.1007/s00234-007-0269-2. View

18.

Lalu M, McIntyre L, Pugliese C, Fergusson D, Winston B, Marshall J . Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012; 7(10):e47559. PMC: 3485008. DOI: 10.1371/journal.pone.0047559. View

19.

Gluckman E, Broxmeyer H, Auerbach A, Friedman H, Douglas G, Devergie A . Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989; 321(17):1174-8. DOI: 10.1056/NEJM198910263211707. View

20.

Noh Y, Lee Y, Seo S, Jeong J, Choi S, Back J . A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities. J Stroke Cerebrovasc Dis. 2013; 23(4):636-42. DOI: 10.1016/j.jstrokecerebrovasdis.2013.06.002. View