<b>Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury</b>

Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative.

Results:

There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation.

Conclusion:

Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

Key words:
Cell- and Tissue-Based Therapy; Spinal Cord Injuries; Dental Pulp; Dogs

Authorship

Matheus Levi Tajra Feitosa

Fellow PhD degree, Postgraduate Program in Anatomy in Domestic and Wild Animals, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, Universidade de São Paulo (USP), Brazil. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data, manuscript preparation.Universidade de São PauloBrazilBrazilFellow PhD degree, Postgraduate Program in Anatomy in Domestic and Wild Animals, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, Universidade de São Paulo (USP), Brazil. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data, manuscript preparation.

Carlos Alberto Palmeira Sarmento

Renato Zonzini Bocabello

Fellow Master degree, Postgraduate Program in Anatomy in Domestic and Wild Animals, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data; manuscript preparation.USPBrazilSao Paulo, SP, BrazilFellow Master degree, Postgraduate Program in Anatomy in Domestic and Wild Animals, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data; manuscript preparation.

Patrícia Cristina Baleeiro Beltrão-Braga

Assistant Professor, Department of Surgery, Stem Cell Laboratory, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study, acquisition of human stem cells, analysis and interpretation of data, manuscript writing.USPBrazilSao Paulo, SP, BrazilAssistant Professor, Department of Surgery, Stem Cell Laboratory, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study, acquisition of human stem cells, analysis and interpretation of data, manuscript writing.

Graciela Conceição Pignatari

PosDoc Fellow, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study, acquisition of human stem cells, analysis and interpretation of data, manuscript writing.USPBrazilSao Paulo, SP, BrazilPosDoc Fellow, Department of Surgery, Faculty of Veterinary Medicine and Animal Science, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study, acquisition of human stem cells, analysis and interpretation of data, manuscript writing.

Robson Fortes Giglio

Assistant Professor, Department of Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data; manuscript preparation and writing.University of FloridaUSAGainesville, Florida, USAAssistant Professor, Department of Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA. Intellectual and scientific content of the study; conception and design of the study; acquisition, analysis and interpretation of data; manuscript preparation and writing.

Maria Angelica Miglino

Researcher, CNPq Grant Level 1A - CA VT, Professor, Chairwoman, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, USP, Pirassunung-SP, Brazil. Conception and design of the study, manuscript writing, critical revision, final approval.USPBrazilPirassunung, SP, BrazilResearcher, CNPq Grant Level 1A - CA VT, Professor, Chairwoman, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, USP, Pirassunung-SP, Brazil. Conception and design of the study, manuscript writing, critical revision, final approval.

Jéssica Rodrigues Orlandin

Fellow Master degree, Postgraduate Program in Animal Bioscience, Laboratory of Stem Cell and Gene Therapy, Veterinary Medicine Department, Faculty of Animal Science and Food Engineering, USP, Pirassununga-SP, Brazil. Manuscript preparation.USPBrazilPirassununga, SP, BrazilFellow Master degree, Postgraduate Program in Animal Bioscience, Laboratory of Stem Cell and Gene Therapy, Veterinary Medicine Department, Faculty of Animal Science and Food Engineering, USP, Pirassununga-SP, Brazil. Manuscript preparation.

Carlos Eduardo Ambrósio

Researcher, CNPq Grant Level 1A - CA VT, Associate Professor III, Head, Department Veterinary Medicine, Laboratory of Stem Cell and Gene Therapy, Veterinary Medicine Department, Faculty of Animal Science and Food Engineering, USP, Pirassununga-SP, Brazil. Conception and design of the study, manuscript writing, critical revision, final approval.USPBrazilPirassununga, SP, BrazilResearcher, CNPq Grant Level 1A - CA VT, Associate Professor III, Head, Department Veterinary Medicine, Laboratory of Stem Cell and Gene Therapy, Veterinary Medicine Department, Faculty of Animal Science and Food Engineering, USP, Pirassununga-SP, Brazil. Conception and design of the study, manuscript writing, critical revision, final approval.

Correspondence: Carlos Eduardo Ambrósio Faculdade de Ciências Animal e Engenharia de Alimentos Departamento de Medicina Veterinária-USP Avenida Duque de Caxias, 225 13635-900 Pirassununga - SP Brasil ceambrosio@usp.br

Conflict of interest:

none

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (5)
Tables (1)

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Figure 1
Procedure for human immature dental pulp stem cell (h-IDPSC) intramedullary injection in dog with chronic spinal cord injury. A. Hemilaminectomy surgical approach for spinal cord. B. Intramedullary injection of h-IDPSC in site of disc compression.

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Figure 2
Case 1 pre-operative MRI. A. White arrow points to central channel dilation. B. White arrow points to ventrolateral extradural compression.

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Figure 3
Case 2 pre and post-operative MRI. A. Central channel dilation. B. Severe ventromedian extradural compressive myelopathy in L4-5. C. Gliosis or focal hemorrhages at T13-L1. D. White arrow points to permanent central channel. E. Right ventrolateral compression.

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Figure 4
Case 3 pre and post-operative MRI evaluation. A. Medullary hypersinal. B. Previous hemilaminectomy surgery. C. Permanent medullary hypersinal. D. Medullary central channel dilation.

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Figure 5
Olby Scale assessment of three dogs with chronic spinal cord injury undergoing human immature dental pulp stem cell transplantation.

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Table 1
Assessment of pelvic limb function by Olby Scale¹⁹19 Olby NJ, De Risio L, Muñana KR, Wosar MA, Skeen TM, Sharp NJ, Keene BW. Development of a functional scoring system in dogs with acute spinal cord injuries. Am J Vet Res. 2001;62(10):1624-8. PMID: 11592330..

Figure 1 Procedure for human immature dental pulp stem cell (h-IDPSC) intramedullary injection in dog with chronic spinal cord injury. A. Hemilaminectomy surgical approach for spinal cord. B. Intramedullary injection of h-IDPSC in site of disc compression.

Figure 2 Case 1 pre-operative MRI. A. White arrow points to central channel dilation. B. White arrow points to ventrolateral extradural compression.

Figure 3 Case 2 pre and post-operative MRI. A. Central channel dilation. B. Severe ventromedian extradural compressive myelopathy in L4-5. C. Gliosis or focal hemorrhages at T13-L1. D. White arrow points to permanent central channel. E. Right ventrolateral compression.

Figure 4 Case 3 pre and post-operative MRI evaluation. A. Medullary hypersinal. B. Previous hemilaminectomy surgery. C. Permanent medullary hypersinal. D. Medullary central channel dilation.

Figure 5 Olby Scale assessment of three dogs with chronic spinal cord injury undergoing human immature dental pulp stem cell transplantation.

Table 1 Assessment of pelvic limb function by Olby Scale¹⁹19 Olby NJ, De Risio L, Muñana KR, Wosar MA, Skeen TM, Sharp NJ, Keene BW. Development of a functional scoring system in dogs with acute spinal cord injuries. Am J Vet Res. 2001;62(10):1624-8. PMID: 11592330..

Stage	Point	Neurological Status
1	0	No pelvic limb movement and no deep pain sensation.
	1	No pelvic limb movement with deep pain sensation.
	2	No pelvic limb movement but voluntary tail movement
2	3	Minimal non-weight-bearing protaction of pelvic limb (movement of one joint)
	4	Non-weight-bearing protaction of pelvic limb with no more than one jt. Involved less than 50% of the time
	5	Non-weight-bearing protaction of pelvic limb with no more than one jt. Involved more than 50% of the time
3	6	Weight-bearing protaction of pelvic limb less than 10% of the time
	7	Weight-bearing protaction of pelvic limb 10-50% of the time.
	8	Weight-bearing protaction of pelvic limb more than 50% of the time.
4	9	Weight-bearing protaction 100% of time with reduced strength of pelvic limb. Mistake> 90% of the time.
	10	Weight-bearing protaction 100% of time with reduced strength of pelvic limb. Mistake 50-90% of the time.
	11	Weight-bearing protaction 100% of time with reduced strength of pelvic limb. Mistake < 50% of the time.
5	12	Ataxic pelvic limb gait with normal strength, but mistakes made > 50% of time.
	13	Ataxic pelvic limb gait with normal strength, but mistakes made < 50% of time.
	14	Normal pelvic limb gait.

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<b>Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury</b>

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[1] Correspondence: Carlos Eduardo Ambrósio Faculdade de Ciências Animal e Engenharia de Alimentos Departamento de Medicina Veterinária-USP Avenida Duque de Caxias, 225 13635-900 Pirassununga - SP Brasil ceambrosio@usp.br