Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses.
Abstract: It is currently unknown if the intrathecal administration of a high dose of allogeneic mesenchymal stem cells (MSCs) is safe, how MSCs migrate throughout the vertebral canal after intrathecal administration, and whether MSCs are able to home to a site of injury. The aims of the study were: 1) to evaluate the safety of intrathecal injection of 100 million allogeneic adipose-derived MSCs (ASCs); 2) to assess the distribution of ASCs after atlanto-occipital (AO) and lumbosacral (LS) injection in healthy horses; and 3) to determine if ASCs homed to the site of injury in neurologically diseased horses. Six healthy horses received 100 × 10 allogeneic ASCs via AO (n = 3) or LS injection (n = 3). For two of these horses, ASCs were radiolabeled with technetium and injected AO (n = 1) or LS (n = 1). Neurological examinations were performed daily, and blood and cerebrospinal fluid (CSF) were evaluated prior to and at 30 days after injection. Scintigraphic images were obtained immediately postinjection and at 30 mins, 1 h, 5 h, and 24 h after injection. Three horses with cervical vertebral compressive myelopathy (CVCM) received 100 × 10 allogeneic ASCs labeled with green fluorescent protein (GFP) via AO injection and were euthanized 1-2 weeks after injection for a full nervous system necropsy. CSF parameters were compared using a paired student's t test. There were no significant alterations in blood, CSF, or neurological examinations at any point after either AO or LS ASC injections into healthy horses. The radioactive signal could be identified all the way to the lumbar area after AO ASC injection. After LS injection, the signal extended caudally but only a minimal radioactive signal extended further cranially. GFP-labeled ASCs were not present at the site of disease at either 1 or 2 weeks following intrathecal administration. The intrathecal injection of allogeneic ASCs was safe and easy to perform in horses. The AO administration of ASCs resulted in better distribution within the entire subarachnoid space in healthy horses. ASCs could not be found after 7 or 15 days of injection at the site of injury in horses with CVCM.
Publication Date: 2018-04-10 PubMed ID: 29631634PubMed Central: PMC5891950DOI: 10.1186/s13287-018-0849-6Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Veterinary
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research paper assesses the safety and tracking of intrathecal administration of allogeneic mesenchymal stem cells in both healthy and diseased horses, their migration through the vertebral canal, and whether they can position themselves at the site of an injury.
Research Objectives
- The research was conducted with three main objectives. Firstly, it aimed to determine the safety of injecting a high dose (100 million) of allogeneic adipose-derived mesenchymal stem cells (ASCs) intrathecally.
- Secondly, the study aimed to observe how these ASCs are distributed after being injected in either the atlanto-occipital (AO) or the lumbosacral (LS) area in healthy horses.
- Finally, the purpose of the study was to ascertain whether the ASCs hone towards the site of injury in horses suffering from neurological diseases.
Study Design and Methods
- In the research, a total of six healthy horses were injected with the allogeneic ASCs. For two out of these six horses, the ASCs were labeled with technetium before being injected either at AO or LS.
- Post this, daily neurological examinations were conducted and the blood and cerebrospinal fluid (CSF) were evaluated before and 30 days post-injection.
- The distribution of these cells was then assessed through scintigraphic images obtained at different intervals after the injection.
- Additionally, three diseased horses suffering from cervical vertebral compressive myelopathy (CVCM) were injected with green fluorescent protein (GFP) labeled ASCs and observed for one to two weeks before being euthanized for a complete nervous system examination.
Results and Findings
- The study concluded that the injection of allogeneic ASCs was safe as there were no significant changes in blood, CSF, or neurological conditions in any of the horses.
- Furthermore, the study found that the radioactive signal of ASCs could be traced to the lumbar area after an AO injection but only minimally after an LS injection.
- However, the ASCs, labeled with GFP, could not be found at the site of disease in diseased horses even after a week or two weeks post-injection, indicating that the ASCs did not necessarily home to the site of injury.
- The paper also noted that the intrathecal injection of ASCs was found to be easily performed in horses and that the AO administration of ASCs led to better distribution within the entire subarachnoid space in healthy horses.
Conclusions
- The research concludes that the intrathecal injection of allogeneic ASCs seems to be safe and can be easily performed in horses.
- However, although ASCs were well distributed within the subarachnoid space in healthy horses after AO administration, ASCs could not be found at the site of injury in horses with CVCM, suggesting that they may not home to the site of injury.
Cite This Article
APA
(2018).
Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses.
Stem Cell Res Ther, 9(1), 96.
https://doi.org/10.1186/s13287-018-0849-6 Publication
Researcher Affiliations
MeSH Terms
- Adipose Tissue / cytology
- Animals
- Cell Movement
- Cells, Cultured
- Cerebrospinal Fluid / cytology
- Female
- Horse Diseases / therapy
- Horses
- Mesenchymal Stem Cell Transplantation / adverse effects
- Mesenchymal Stem Cell Transplantation / methods
- Mesenchymal Stem Cell Transplantation / veterinary
- Mesenchymal Stem Cells / physiology
- Random Allocation
- Spinal Cord Compression / therapy
- Spinal Cord Compression / veterinary
- Transplantation, Homologous
Conflict of Interest Statement
ETHICS APPROVAL: The protocol (#18785, #18801) was reviewed and approved by the UC Davis IACUC on 2 June 2015. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
This article includes 67 references
- Laroni A, de Rosbo NK, Uccelli A. Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection.. Immunol Lett 2015 Dec;168(2):183-90.
- Wang S, Cheng H, Dai G, Wang X, Hua R, Liu X, Wang P, Chen G, Yue W, An Y. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury.. Brain Res 2013 Sep 26;1532:76-84.
- Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis.. Arthritis Res Ther 2012 Feb 7;14(1):R31.
- Xia P, Wang X, Lin Q, Li X. Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis.. Int Orthop 2015 Dec;39(12):2363-72.
- Nöth U, Rackwitz L, Steinert AF, Tuan RS. Cell delivery therapeutics for musculoskeletal regeneration.. Adv Drug Deliv Rev 2010 Jun 15;62(7-8):765-83.
- Zeira O, Asiag N, Aralla M, Ghezzi E, Pettinari L, Martinelli L, Zahirpour D, Dumas MP, Lupi D, Scaccia S, Konar M, Cantile C. Adult autologous mesenchymal stem cells for the treatment of suspected non-infectious inflammatory diseases of the canine central nervous system: safety, feasibility and preliminary clinical findings.. J Neuroinflammation 2015 Sep 29;12:181.
- Dang S, Xu H, Xu C, Cai W, Li Q, Cheng Y, Jin M, Wang RX, Peng Y, Zhang Y, Wu C, He X, Wan B, Zhang Y. Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis.. Autophagy 2014 Jul;10(7):1301-15.
- Liu M, Zeng X, Wang J, Fu Z, Wang J, Liu M, Ren D, Yu B, Zheng L, Hu X, Shi W, Xu J. Immunomodulation by mesenchymal stem cells in treating human autoimmune disease-associated lung fibrosis.. Stem Cell Res Ther 2016 Apr 23;7(1):63.
- Singh UP, Singh NP, Singh B, Mishra MK, Nagarkatti M, Nagarkatti PS, Singh SR. Stem cells as potential therapeutic targets for inflammatory bowel disease.. Front Biosci (Schol Ed) 2010 Jun 1;2(3):993-1008.
- Karussis D, Petrou P, Kassis I. Clinical experience with stem cells and other cell therapies in neurological diseases.. J Neurol Sci 2013 Jan 15;324(1-2):1-9.
- Silver J, Schwab ME, Popovich PG. Central nervous system regenerative failure: role of oligodendrocytes, astrocytes, and microglia.. Cold Spring Harb Perspect Biol 2014 Dec 4;7(3):a020602.
- Tam RY, Fuehrmann T, Mitrousis N, Shoichet MS. Regenerative therapies for central nervous system diseases: a biomaterials approach.. Neuropsychopharmacology 2014 Jan;39(1):169-88.
- Glavaski-Joksimovic A, Bohn MC. Mesenchymal stem cells and neuroregeneration in Parkinson's disease.. Exp Neurol 2013 Sep;247:25-38.
- Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke.. Stem Cells 2010 Jun;28(6):1099-106.
- Kerkis I, Haddad MS, Valverde CW, Glosman S. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.. Stem Cell Res Ther 2015 Dec 14;6:232.
- Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, Testa L, Stecco A, Tarletti R, Miglioretti M, Fava E, Nasuelli N, Cisari C, Massara M, Vercelli R, Oggioni GD, Carriero A, Cantello R, Monaco F, Fagioli F. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.. Exp Neurol 2010 May;223(1):229-37.
- Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, Yang YS, Suh JG, Lee BH, Jin HK, Bae JS. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation.. Neurobiol Aging 2012 Mar;33(3):588-602.
- Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis.. J Neurol Sci 2012 Feb 15;313(1-2):167-77.
- Yousefifard M, Nasirinezhad F, Shardi Manaheji H, Janzadeh A, Hosseini M, Keshavarz M. Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model.. Stem Cell Res Ther 2016 Mar 8;7:36.
- Reed S, Grant B, Nout Y. Cervical vertebral stenotic myelopathy. In: Furr M, Reed S, editors. Equine neurology. Hoboken: Blackwell Publishing Ltd; 2008. p. 283–98.
- Cole C, Bentz B. Treatment of equine nervous system disorders. In: Cole C, Bentz B, Maxwell L, editors. John Wiley & Sons, Inc; 2014. p. 192–217.
- Dubey JP, Howe DK, Furr M, Saville WJ, Marsh AE, Reed SM, Grigg ME. An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM).. Vet Parasitol 2015 Apr 15;209(1-2):1-42.
- Reed SM, Furr M, Howe DK, Johnson AL, MacKay RJ, Morrow JK, Pusterla N, Witonsky S. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention.. J Vet Intern Med 2016 Mar-Apr;30(2):491-502.
- Hu DZ, Zhou LF, Zhu JH. Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function.. Chin Med J (Engl) 2004 Oct;117(10):1576-8.
- Liu J, Han D, Wang Z, Xue M, Zhu L, Yan H, Zheng X, Guo Z, Wang H. Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells.. Cytotherapy 2013 Feb;15(2):185-91.
- Jung DI, Ha J, Kang BT, Kim JW, Quan FS, Lee JH, Woo EJ, Park HM. A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury.. J Neurol Sci 2009 Oct 15;285(1-2):67-77.
- Chen BK, Staff NP, Knight AM, Nesbitt JJ, Butler GW, Padley DJ, Parisi JE, Dietz AB, Windebank AJ. A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting Phase I human trials.. Transfusion 2015 May;55(5):1013-20.
- Maia L, da Cruz Landim-Alvarenga F, Taffarel MO, de Moraes CN, Machado GF, Melo GD, Amorim RM. Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses.. BMC Vet Res 2015 Mar 15;11:63.
- Mayhew IG. Collection of cerebrospinal fluid from the horse.. Cornell Vet 1975 Oct;65(4):500-11.
- Pease A, Behan A, Bohart G. Ultrasound-guided cervical centesis to obtain cerebrospinal fluid in the standing horse.. Vet Radiol Ultrasound 2012 Jan-Feb;53(1):92-5.
- Lunn DP, Mayhew IG. The neurological evaluation of horses. Equine Vet Educ 1989;1:94–101.
- Zhang J, Huang X, Wang H, Liu X, Zhang T, Wang Y, Hu D. The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy.. Stem Cell Res Ther 2015 Dec 1;6:234.
- Pusterla N, Tamez-Trevino E, White A, Vangeem J, Packham A, Conrad PA, Kass P. Comparison of prevalence factors in horses with and without seropositivity to Neospora hughesi and/or Sarcocystis neurona.. Vet J 2014 May;200(2):332-4.
- Johnson AL, Morrow JK, Sweeney RW. Indirect fluorescent antibody test and surface antigen ELISAs for antemortem diagnosis of equine protozoal myeloencephalitis.. J Vet Intern Med 2013 May-Jun;27(3):596-9.
- Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL. Comparative Analysis of the Immunomodulatory Properties of Equine Adult-Derived Mesenchymal Stem Cells().. Cell Med 2012;4(1):1-11.
- Meyerrose TE, Roberts M, Ohlemiller KK, Vogler CA, Wirthlin L, Nolta JA, Sands MS. Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplantation model of human disease.. Stem Cells 2008 Jul;26(7):1713-22.
- Sole A, Spriet M, Galuppo LD, Padgett KA, Borjesson DL, Wisner ER, Brosnan RJ, Vidal MA. Scintigraphic evaluation of intra-arterial and intravenous regional limb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal limb using (99m) Tc-HMPAO.. Equine Vet J 2012 Sep;44(5):594-9.
- Spriet M, Hunt GB, Walker NJ, Borjesson DL. Scintigraphic tracking of mesenchymal stem cells after portal, systemic intravenous and splenic administration in healthy beagle dogs.. Vet Radiol Ultrasound 2015 May-Jun;56(3):327-34.
- Meyerrose TE, De Ugarte DA, Hofling AA, Herrbrich PE, Cordonnier TD, Shultz LD, Eagon JC, Wirthlin L, Sands MS, Hedrick MA, Nolta JA. In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models.. Stem Cells 2007 Jan;25(1):220-7.
- Bauer G, Dao MA, Case SS, Meyerrose T, Wirthlin L, Zhou P, Wang X, Herrbrich P, Arevalo J, Csik S, Skelton DC, Walker J, Pepper K, Kohn DB, Nolta JA. In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors.. Mol Ther 2008 Jul;16(7):1308-15.
- Owens SD, Kol A, Walker NJ, Borjesson DL. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses.. Stem Cells Int 2016;2016:5830103.
- Gershwin LJ, Netherwood KA, Norris MS, Behrens NE, Shao MX. Equine IgE responses to non-viral vaccine components.. Vaccine 2012 Dec 14;30(52):7615-20.
- Levine JM, Ngheim PP, Levine GJ, Cohen ND. Associations of sex, breed, and age with cervical vertebral compressive myelopathy in horses: 811 cases (1974-2007).. J Am Vet Med Assoc 2008 Nov 1;233(9):1453-8.
- Satti HS, Waheed A, Ahmed P, Ahmed K, Akram Z, Aziz T, Satti TM, Shahbaz N, Khan MA, Malik SA. Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study.. Cytotherapy 2016 Apr;18(4):518-22.
- Villanova M, Bach JR. Allogeneic mesenchymal stem cell therapy outcomes for three patients with spinal muscular atrophy type 1.. Am J Phys Med Rehabil 2015 May;94(5):410-5.
- Liang J, Zhang H, Hua B, Wang H, Wang J, Han Z, Sun L. Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis.. Mult Scler 2009 May;15(5):644-6.
- Pezzanite LM, Fortier LA, Antczak DF, Cassano JM, Brosnahan MM, Miller D, Schnabel LV. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.. Stem Cell Res Ther 2015 Apr 12;6(1):54.
- Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease.. Regen Med 2010 Nov;5(6):933-46.
- Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, Burkhardt U, Proksch B, Verleysdonk S, Ayturan M, Buniatian GH, Gleiter CH, Frey WH 2nd. Intranasal delivery of cells to the brain.. Eur J Cell Biol 2009 Jun;88(6):315-24.
- Shyu WC, Lin SZ, Chiang MF, Su CY, Li H. Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats.. J Neurosci 2006 Mar 29;26(13):3444-53.
- Jarocha D, Milczarek O, Wedrychowicz A, Kwiatkowski S, Majka M. Continuous improvement after multiple mesenchymal stem cell transplantations in a patient with complete spinal cord injury.. Cell Transplant 2015;24(4):661-72.
- Sahraian MA, Mohyeddin Bonab M, Ahmadi Karvigh S, Yazdanbakhsh S, Nikbin B, Lotfi J. Intrathecal mesenchymal stem cell therapy in multiple sclerosis: a follow-up study for five years after injection. Arch Neurosci 2014;1:71–75.
- Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders.. Nature 2006 Jun 29;441(7097):1094-6.
- Cohen JA. Mesenchymal stem cell transplantation in multiple sclerosis.. J Neurol Sci 2013 Oct 15;333(1-2):43-9.
- Kishk NA, Abokrysha NT, Gabr H. Possible induction of acute disseminated encephalomyelitis (ADEM)-like demyelinating illness by intrathecal mesenchymal stem cell injection.. J Clin Neurosci 2013 Feb;20(2):310-2.
- Johnson PJ, Constantinescu GM. Collection of cerebrospinal fluid in horses. Equine Vet Educ 2000;12:7–12.
- Aleman M, Borchers A, Kass PH, Puchalski SM. Ultrasound-assisted collection of cerebrospinal fluid from the lumbosacral space in equids.. J Am Vet Med Assoc 2007 Feb 1;230(3):378-84.
- Schwarz B, Piercy RJ. Cerebrospinal fluid collection and its analysis in equine neurological disease. Equine Vet Educ 2006;18:243–248.
- Audigié F, Tapprest J, Didierlaurent D, Denoix JM. Ultrasound-guided atlanto-occipital puncture for myelography in the horse.. Vet Radiol Ultrasound 2004 Jul-Aug;45(4):340-4.
- Sole A, Spriet M, Padgett KA, Vaughan B, Galuppo LD, Borjesson DL, Wisner ER, Vidal MA. Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.. Equine Vet J 2013 Nov;45(6):726-31.
- Vernau W, Vernau KA, Sue Bailey C. Cerebrospinal fluid. In: Kaneko J, Harvey JW, Bruss ML, editors. Clinical biochemistry of domestic animals. 6. San Diego: Academic Press; 2008. pp. 769–819.
- Carvalho AM, Yamada AL, Golim MA, Álvarez LE, Hussni CA, Alves AL. Evaluation of mesenchymal stem cell migration after equine tendonitis therapy.. Equine Vet J 2014 Sep;46(5):635-8.
- Lin P, Correa D, Kean TJ, Awadallah A, Dennis JE, Caplan AI. Serial transplantation and long-term engraftment of intra-arterially delivered clonally derived mesenchymal stem cells to injured bone marrow.. Mol Ther 2014 Jan;22(1):160-8.
- Li Y, Lin F. Mesenchymal stem cells are injured by complement after their contact with serum.. Blood 2012 Oct 25;120(17):3436-43.
- Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, von Bonin M, Barbieri L, Halai K, Ward S, Weng L, Chakraverty R, Lombardi G, Watt FM, Orchard K, Marks DI, Apperley J, Bornhauser M, Walczak H, Bennett C, Dazzi F. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation.. Sci Transl Med 2017 Nov 15;9(416).
- Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting.. Blood 2006 Sep 15;108(6):2114-20.
- Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.. Cell Stem Cell 2009 Jul 2;5(1):54-63.
Citations
This article has been cited 16 times.- Greco A, Meomartino L, Gnudi G, Brunetti A, Di Giancamillo M. Imaging techniques in veterinary medicine. Part II: Computed tomography, magnetic resonance imaging, nuclear medicine.. Eur J Radiol Open 2023;10:100467.
- Vives J, Hernández J, Mirabel C, Puigdomenech-Poch M, Romeo-Guitart D, Marmolejo-Martínez-Artesero S, Cabrera-Pérez R, Jaramillo J, Kumru H, García-López J, Vidal-Samsó J, Navarro X, Coll-Bonet R. Preclinical Development of a Therapy for Chronic Traumatic Spinal Cord Injury in Rats Using Human Wharton's Jelly Mesenchymal Stromal Cells: Proof of Concept and Regulatory Compliance.. Cells 2022 Jul 8;11(14).
- Maric DM, Velikic G, Maric DL, Supic G, Vojvodic D, Petric V, Abazovic D. Stem Cell Homing in Intrathecal Applications and Inspirations for Improvement Paths.. Int J Mol Sci 2022 Apr 13;23(8).
- Johnson JP, Vinardell T, David F. Ultrasound-guided injections of the equine head and neck: review and expert opinion.. J Equine Sci 2021 Dec;32(4):103-115.
- Benavides FP, Pinto GBA, Heckler MCT, Hurtado DMR, Teixeira LR, Monobe MMS, Machado GF, de Melo GD, Rodríguez-Sánchez DN, Alvarenga FDCLE, Amorim RM. Intrathecal Transplantation of Autologous and Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Dogs.. Cell Transplant 2021 Jan-Dec;30:9636897211034464.
- Beerts C, Brondeel C, Pauwelyn G, Depuydt E, Tack L, Duchateau L, Xu Y, Saunders JH, Peremans K, Spaas JH. Scintigraphic tracking of (99m)Technetium-labelled equine peripheral blood-derived mesenchymal stem cells after intravenous, intramuscular, and subcutaneous injection in healthy dogs.. Stem Cell Res Ther 2021 Jul 13;12(1):393.
- Sanchez-Diaz M, Quiñones-Vico MI, Sanabria de la Torre R, Montero-Vílchez T, Sierra-Sánchez A, Molina-Leyva A, Arias-Santiago S. Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review.. J Clin Med 2021 Jun 29;10(13).
- Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses.. Animals (Basel) 2021 Mar 25;11(4).
- Enciso N, Avedillo L, Fermín ML, Fragío C, Tejero C. Cutaneous wound healing: canine allogeneic ASC therapy.. Stem Cell Res Ther 2020 Jun 29;11(1):261.
- Mocchi M, Dotti S, Bue MD, Villa R, Bari E, Perteghella S, Torre ML, Grolli S. Veterinary Regenerative Medicine for Musculoskeletal Disorders: Can Mesenchymal Stem/Stromal Cells and Their Secretome Be the New Frontier?. Cells 2020 Jun 11;9(6).
- Dos Santos Machado JJ, Piñeiro BG, Ramos IP, de Souza SAL, Gutfilen B, Nicola MH, de Souza PRC, Cruz E, Goldenberg RC. Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study.. Stem Cells Int 2020;2020:1823427.
- Kim H, Na DL, Lee NK, Kim AR, Lee S, Jang H. Intrathecal Injection in A Rat Model: A Potential Route to Deliver Human Wharton's Jelly-Derived Mesenchymal Stem Cells into the Brain.. Int J Mol Sci 2020 Feb 13;21(4).
- MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.. Front Vet Sci 2019;6:507.
- You Y, Wen DG, Gong JP, Liu ZJ. Research Status of Mesenchymal Stem Cells in Liver Transplantation.. Cell Transplant 2019 Dec;28(12):1490-1506.
- Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.. Vet Ophthalmol 2020 Jan;23(1):160-170.
- Thomson AL, Berent AC, Weisse C, Langston CE. Intra-arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: Phase I clinical trial.. J Vet Intern Med 2019 May;33(3):1353-1361.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists