Abstract
Because of the important role of preclinical animal studies in the development of innovative medicines for human patients, many stem cell therapies have been evaluated in animals. However, the last decade has seen the beginning of a shift from stem cell treatments in animals only for the benefit of human patients to including new therapeutic development of tissue stem cells primarily for animal care. Not surprisingly, given their historical dependency, the new field of veterinary stem cell medicine faces many of the same challenges as human stem cell medicine. In this chapter, a shared major deficiency, the lack of stem cell-specific dosing, is considered from the perspective that implementing dosing would accelerate progress in veterinary stem cell medicine and human stem cell medicine as well, as a follow-on. Since the vast majority of present-day veterinary stem cell treatments utilize preparations of mesenchymal stem cells (MSCs), the well-recognized uncertainties about this treatment source are discussed. The challenges of quantifying the stem cell-specific dose of MSC preparations exemplify the general problem of determining the stem cell dose of all stem cell treatments. Particular consideration is given to previous veterinary MSC treatment studies that include measures that might relate to stem cell dosage. Kinetic stem cell counting, a first potential solution to the tissue stem cell dosing problem, is described, and the potential benefits of its future use are discussed. Adoption of kinetic stem cell counting into the general practice of veterinary stem cell medicine is presented as the key that can unlock the full potential of stem cells in veterinary medical practice and perhaps human stem cell medical practice as well.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Almeida-Porada G, Porada CD, Chamberlain J et al (2004) Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 104(8):2582–2590. https://doi.org/10.1182/blood-2004-01-0259
Arzi B, Peralta S, Fiani N et al (2020) A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis. Stem Cell Res Ther 11(1):115. https://doi.org/10.1186/s13287-020-01623-9
Barberini DJ, Aleman M, Aristizabal F et al (2018) Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses. Stem Cell Res Ther 9:96. https://doi.org/10.1186/s13287-018-0849-6
Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255:197–200
Caplan AI (2017) Mesenchymal stem cells: time to change the name! Stem Cells Transl Med 6:1445–1451. https://doi.org/10.1002/sctm.17-0051
Capuco AV, Choudhary RK (2020) Symposium review: determinants of milk production: understanding population dynamics in the bovine mammary epithelium. J Dairy Sci 103(3):2928–2940. https://doi.org/10.3168/jds.2019-17241
Choudhary RK, Capuco AV (2012) In vitro expansion of mammary stem/progenitor cell population by xanthosine treatment. BMC Cell Biol 13:14. https://doi.org/10.1186/1471-2121-13-14
Costa CRM, Feitosa MLT, Rocha AR et al (2019) Adipose stem cells in reparative goat mastitis mammary gland. PLoS One 14(10):e0223751. https://doi.org/10.1371/journal.pone.0223751
Delco ML, Goodale M, Talts JF et al (2020) Integrin α10β1-selected mesenchymal stem cells mitigate the progression of osteoarthritis in an equine talar impact model. Am J Sports Med 48(3):612–623. https://doi.org/10.1177/0363546519899087
Devireddy LR, Myers M, Screven R et al (2019) A serum-free medium formulation efficiently supports isolation and propagation of canine adipose-derived mesenchymal stem/stromal cells. PLoS One 14(2):e0210250. https://doi.org/10.1371/journal.pone.0210250
Dutton R, Abdi F, Minnetyan L et al (2020) A computational technology for specific counting of perinatal and postnatal human tissue stem cells for transplantation medicine. OBM Transplant 4(3):24. https://doi.org/10.21926/obm.transplant.2003117
Gallant.com (2019–2020) https://gallant.com/science-library/
Gnecchi M, Danieli P, Malpasso G et al (2016) Paracrine mechanisms of mesenchymal stem cells in tissue repair. Methods Mol Biol 1416:123–146. https://doi.org/10.1007/978-1-4939-3584-0_7
Gomez-Salazar M, Gonzalez-Calofre ZN, Casamitjana J et al (2020) Five decades later, are mesenchymal stem cells still relevant? Front Bioeng Biotechnol 8:148. https://doi.org/10.3389/fbioe.2020.00148
Gugjoo MB, Amarpal, Chandra V et al (2018) Mesenchymal stem cell research in veterinary medicine. Curr Stem Cell Res Ther 13(8):645–657. https://doi.org/10.2174/1574888X13666180517074444
Huh YH, Noh M, Burden F et al (2015) Use of sparse feature bioinformatics to identify a novel pattern-specific biomarker for counting asymmetrically self-renewing distributed stem cells. Stem Cell Res 14:144–154. https://doi.org/10.1016/j.scr.2014.12.007
Ivanovic Z (2010) Hematopoietic stem cells in research and clinical applications: the “CD34 issue”. World J Stem Cells 2:18–23
Kang MH, Park HM (2020) Challenges of stem cell therapies in companion animal practice. J Vet Sci 21(3):e42. https://doi.org/10.4142/jvs.2020.21.e42jvs-21-e42
Kavanagh DP, Kalia N (2011) Hematopoietic stem cell homing to injured tissues. Stem Cell Rev Rep 7(3):672–682. https://doi.org/10.1007/s12015-011-9240-z
Li MD, Atkins H, Bubela T (2014) The global landscape of stem cell clinical trials. Regen Med 9(1):27–39. https://doi.org/10.2217/rme.13.80
Liesveld JL, Sharma N, Aljitawi OS (2020) Stem cell homing: from physiology to therapeutics. Stem Cells 38(10):1241–1253. https://doi.org/10.1002/stem.3242. Epub 2020 Jul 21
Liu Z, Screven R, Boxer L et al (2018) Characterization of canine adipose-derived mesenchymal stromal/stem cells in serum-free medium. Tissue Eng Part C Methods 24(7):399–411. https://doi.org/10.1089/ten.TEC.2017.0409
Nitzsche F, Müller C, Lukomska B (2017) Concise review: MSC adhesion cascade-insights into homing and transendothelial migration. Stem Cells 35(6):1446–1460. https://doi.org/10.1002/stem.2614
Panchalingam K, Jacox L, Cappiello BD et al (2020) Non-random sister chromatid segregation in human tissue stem cells. Symmetry 12:1868. https://doi.org/10.3390/sym12111868
Paré J-F, Sherley JL (2006) Biological principles for ex vivo adult stem cell expansion. In: Schatten G (ed) Current topics in developmental biology, vol 73. Elsevier, Inc, San Diego, pp 141–171
Patterson J, Moore CH, Palser E et al (2015) Detecting primitive hematopoietic stem cells in total nucleated and mononuclear cell fractions from umbilical cord blood segments and units. J Transl Med 13:94. https://doi.org/10.1186/s12967-015-0434-z
Pittenger MF, Discher DE, Peault BM et al (2019) Mesenchymal stem cell perspective: cell biology to clinical progress. Regen Med 4:22. https://doi.org/10.1038/s41536-019-0083-6
Purton LE, Scadden DT (2007) Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell 1:263–270
Quimby JM, Borjesson DL (2018) Mesenchymal stem cell therapy in cats: current knowledge and future potential. J Feline Med Surg 20(3):208–216. https://doi.org/10.1177/1098612X18758590
Rich IN (2015) Improving quality and potency testing for umbilical cord blood: a new perspective. Stem Cells Transl Med 4:967–973
Russell KA, Chow NHC, Dukoff D et al (2016) Characterization and immunomodulatory effects of canine adipose tissue- and bone marrow-derived mesenchymal stromal cells. PLoS One 11(12):e0167442. https://doi.org/10.1371/journal.pone.0167442
Saldinger LK, Nelson SG, Bellone RR et al (2020) Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro. Vet Ophthalmol 23(1):160–170. https://doi.org/10.1111/vop.12704
Shakouri-Motlagh A, O’Connor AJ, Brennecke SP et al (2017) Native and solubilized decellularized extracellular matrix: a critical assessment of their potential for improving the expansion of mesenchymal stem cells. Acta Biomater 55:1–12. https://doi.org/10.1016/j.actbio.2017.04.014
Sherley JL (2005) Asymmetric self-renewal: the mark of the adult stem cell. In: Habib NA, Gordon MY, Levicar N, Jiao L, Thomas-Black G (eds) Stem cell repair and regeneration. Imperial College Press, London, pp 21–28
Sherley JL (2006) Mechanisms of genetic fidelity in mammalian adult stem cells. In: Potten CS, Clarke RB, Wilson J, Renehan AG (eds) Tissue stem cells. Taylor Francis, New York, pp 37–54
Sherley JL (2013) New cancer diagnostics and therapeutics from a 9th “hallmark of cancer”: symmetric self-renewal by mutated distributed stem cells. Expert Rev Mol Diagn 13:797–810
Sherley JL (2014) Accelerating progress in regenerative medicine by advancing distributed stem cell-based normal human cell biomanufacturing. Pharm Anal Acta 5:286. https://doi.org/10.4172/2153-2435.1000286
Sherley JL (2018a) Dose determination for stem cell medicine: a need whose time has come. In: Atala A, Cetrulo C, Cetrulo K, Murphy SV, Taghizadeh R (eds) Perinatal stem cells: research and therapy. Elsevier, Amsterdam, pp 383–397
Sherley JL (2018b) Stem cell therapy: resolving the mismatch. Pharmaceutical manufacturing. pp 38–41
Standards Coordinating Body (2020) C25 Clinical trial interpretation with unknown cell-specific doses. In: Community perspectives: needed standards in regenerative medicine. p 83. https://static1.squarespace.com/static/58a331b0db29d63c7fb64528/t/5fdcd93257b8971cd7ab4ef2/1608309045242/NeededStandardsReportDecember2020.pdf
Szydlak R (2019) Mesenchymal stem cells’ homing and cardiac tissue repair. Acta Biochim Pol 66(4):483–489. https://doi.org/10.18388/abp.2019_2890
Taghizadeh RR, Sherley JL (2009) Expanding the therapeutic potential of umbilical cord blood hematopoietic stem cells. In: Cetrulo CL, Cetrulo KJ, Cetrulo CL Jr (eds) Perinatal stem cells. Wiley-Blackwell, Hoboken, pp 21–40
Taguchi T, Borjesson DL, Osmond C et al (2019) Influence of donor’s age on immunomodulatory properties of canine adipose tissue-derived mesenchymal stem cells. Stem Cell Dev 28(23):1562–1571. https://doi.org/10.1089/scd.2019.0118
Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222
White JL, Walker NJ, Hu JC et al (2018) A comparison of bone marrow and cord blood mesenchymal stem cells for cartilage self-assembly. Tissue Eng Part A 24(15–16):1262–1272. https://doi.org/10.1089/ten.TEA.2017.0424
Zhan XS, El-Ashram S, Luo DZ et al (2019) A comparative study of biological characteristics and transcriptome profiles of mesenchymal stem cells from different canine tissues. Int J Mol Sci 20(6):1485. https://doi.org/10.3390/ijms20061485
Acknowledgments
Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R43HL154900. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Boutin, S.R., Sherley, J.L. (2021). Advancing Quantitative Stem Cell Dosing for Veterinary Stem Cell Medicine. In: Choudhary, R.K., Choudhary, S. (eds) Stem Cells in Veterinary Science. Springer, Singapore. https://doi.org/10.1007/978-981-16-3464-2_12
Download citation
DOI: https://doi.org/10.1007/978-981-16-3464-2_12
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-3463-5
Online ISBN: 978-981-16-3464-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)