Human Adult Dental Pulp Stem Cells Enhance Poststroke Functional Recovery Through Non-neural Replacement Mechanisms

Overview

Journal Stem Cells Transl Med

Publisher Oxford University Press

Specialties Cell Biology
Pharmacology

Date 2012 Dec 1

PMID 23197777

Citations 87

Authors

Wai Khay Leong

Tanya L Henshall

Agnes Arthur

Karlea L Kremer

Martin D Lewis

Stephen C Helps

John Field

Monica A Hamilton-Bruce

Scott Warming

Jim Manavis

Robert Vink

Stan Gronthos

Simon A Koblar

Affiliations

Soon will be listed here.

Abstract

Human adult dental pulp stem cells (DPSCs), derived from third molar teeth, are multipotent and have the capacity to differentiate into neurons under inductive conditions both in vitro and following transplantation into the avian embryo. In this study, we demonstrate that the intracerebral transplantation of human DPSCs 24 hours following focal cerebral ischemia in a rodent model resulted in significant improvement in forelimb sensorimotor function at 4 weeks post-treatment. At this time, 2.3 ± 0.7% of engrafted cells had survived in the poststroke brain and demonstrated targeted migration toward the stroke lesion. In the peri-infarct striatum, transplanted DPSCs differentiated into astrocytes in preference to neurons. Our data suggest that the dominant mechanism of action underlying DPSC treatment that resulted in enhanced functional recovery is unlikely to be due to neural replacement. Functional improvement is more likely to be mediated through DPSC-dependent paracrine effects. This study provides preclinical evidence for the future use of human DPSCs in cell therapy to improve outcome in stroke patients.

Citing Articles

B2M or CIITA knockdown decreased the alloimmune response of dental pulp stem cells: an in vitro study.

Hu M, Zhang Y, Liu J, Chen Y, Kang J, Zhong J Stem Cell Res Ther. 2024; 15(1):425.

PMID: 39538338 PMC: 11562604. DOI: 10.1186/s13287-024-04023-5.

Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.

Shan Y, Zhang M, Tao E, Wang J, Wei N, Lu Y Signal Transduct Target Ther. 2024; 9(1):242.

PMID: 39271680 PMC: 11399464. DOI: 10.1038/s41392-024-01936-8.

Molars to Medicine: A Focused Review on the Pre-Clinical Investigation and Treatment of Secondary Degeneration following Spinal Cord Injury Using Dental Stem Cells.

Jenkner S, Clark J, Gronthos S, OHare Doig R Cells. 2024; 13(10.

PMID: 38786039 PMC: 11119219. DOI: 10.3390/cells13100817.

Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains.

Kanemura Y, Yamamoto A, Katsuma A, Fukusumi H, Shofuda T, Kanematsu D Cells. 2024; 13(8.

PMID: 38667286 PMC: 11048851. DOI: 10.3390/cells13080671.

Priming and Combined Strategies for the Application of Mesenchymal Stem Cells in Ischemic Stroke: A Promising Approach.

Tian H, Tian F, Ma D, Xiao B, Ding Z, Zhai X Mol Neurobiol. 2024; 61(9):7127-7150.

PMID: 38366307 DOI: 10.1007/s12035-024-04012-y.

References

Gronthos S, Brahim J, Li W, Fisher L, Cherman N, Boyde A . Stem cell properties of human dental pulp stem cells. J Dent Res. 2002; 81(8):531-5. DOI: 10.1177/154405910208100806. View

Bouet V, Boulouard M, Toutain J, Divoux D, Bernaudin M, Schumann-Bard P . The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice. Nat Protoc. 2009; 4(10):1560-4. DOI: 10.1038/nprot.2009.125. View

Cetinalp Demircan P, Eker Sariboyaci A, Unal Z, Gacar G, Subasi C, Karaoz E . Immunoregulatory effects of human dental pulp-derived stem cells on T cells: comparison of transwell co-culture and mixed lymphocyte reaction systems. Cytotherapy. 2011; 13(10):1205-20. DOI: 10.3109/14653249.2011.605351. View

Aspey B, Cohen S, Patel Y, Terruli M, Harrison M . Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke. Neuropathol Appl Neurobiol. 1999; 24(6):487-97. DOI: 10.1046/j.1365-2990.1998.00146.x. View

Chopp M, Li Y, Zhang J . Plasticity and remodeling of brain. J Neurol Sci. 2007; 265(1-2):97-101. DOI: 10.1016/j.jns.2007.06.013. View

Martino G, Pluchino S . The therapeutic potential of neural stem cells. Nat Rev Neurosci. 2006; 7(5):395-406. DOI: 10.1038/nrn1908. View

Takahashi K, Yasuhara T, Shingo T, Muraoka K, Kameda M, Takeuchi A . Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells. Brain Res. 2008; 1234:172-82. DOI: 10.1016/j.brainres.2008.07.086. View

Wada N, Menicanin D, Shi S, Bartold P, Gronthos S . Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol. 2009; 219(3):667-76. DOI: 10.1002/jcp.21710. View

Nosrat I, Widenfalk J, Olson L, Nosrat C . Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury. Dev Biol. 2002; 238(1):120-32. DOI: 10.1006/dbio.2001.0400. View

10.

Matsushita K, Motani R, Sakuta T, Yamaguchi N, Koga T, Matsuo K . The role of vascular endothelial growth factor in human dental pulp cells: induction of chemotaxis, proliferation, and differentiation and activation of the AP-1-dependent signaling pathway. J Dent Res. 2000; 79(8):1596-603. DOI: 10.1177/00220345000790081201. View

11.

Spratt N, Fernandez J, Chen M, Rewell S, Cox S, van Raay L . Modification of the method of thread manufacture improves stroke induction rate and reduces mortality after thread-occlusion of the middle cerebral artery in young or aged rats. J Neurosci Methods. 2006; 155(2):285-90. DOI: 10.1016/j.jneumeth.2006.01.020. View

12.

dAquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A . Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ. 2007; 14(6):1162-71. DOI: 10.1038/sj.cdd.4402121. View

13.

Hamm R, Pike B, ODell D, Lyeth B, JENKINS L . The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma. 1994; 11(2):187-96. DOI: 10.1089/neu.1994.11.187. View

14.

Bederson J, Pitts L, Tsuji M, Nishimura M, Davis R, Bartkowski H . Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986; 17(3):472-6. DOI: 10.1161/01.str.17.3.472. View

15.

Kerkis I, Ambrosio C, Kerkis A, Martins D, Zucconi E, Fonseca S . Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?. J Transl Med. 2008; 6:35. PMC: 2529267. DOI: 10.1186/1479-5876-6-35. View

16.

Locatelli F, Bersano A, Ballabio E, Lanfranconi S, Papadimitriou D, Strazzer S . Stem cell therapy in stroke. Cell Mol Life Sci. 2008; 66(5):757-72. PMC: 11131442. DOI: 10.1007/s00018-008-8346-1. View

17.

Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H . A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp. Stem Cells. 2008; 26(9):2408-18. DOI: 10.1634/stemcells.2008-0393. View

18.

Savitz S, Chopp M, Deans R, Carmichael T, Phinney D, Wechsler L . Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II. Stroke. 2011; 42(3):825-9. DOI: 10.1161/STROKEAHA.110.601914. View

19.

Imitola J, Raddassi K, Park K, Mueller F, Nieto M, Teng Y . Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A. 2004; 101(52):18117-22. PMC: 536055. DOI: 10.1073/pnas.0408258102. View

20.

Waddington R, Youde S, Lee C, Sloan A . Isolation of distinct progenitor stem cell populations from dental pulp. Cells Tissues Organs. 2008; 189(1-4):268-74. DOI: 10.1159/000151447. View