TY - JOUR
T1 - Characterisation and in Vivo Safety of Canine Adipose-Derived Stem Cells
AU - Berziņš, Uldis
AU - Matise-VanHoutana, Ilze
AU - Petersone, Ilze
AU - Duritis, Ilmars
AU - Ņikuļšins, Sergejs
AU - Bogdanova-Jatniece, Ance
AU - Kalis, Martiņš
AU - Svirskis, Šimons
AU - Skrastiņa, Dace
AU - Ezerta, Agnese
AU - Kozlovska, Tatjana
N1 - Funding Information:
This work was supported by the grants No. 10.0014 and No. 09.1283 of the Latvian Council of Science.
Publisher Copyright:
© 2018 Uldis Berziņš et al., published by Sciendo.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - The study characterises canine adipose-derived stem cells (cASCs) in comparison to human ASCs (hASCs) and tests their safety in a canine model after intravenous administration. cASCs from two dogs were cultured under hypoxic conditions in a medium supplemented with autologous serum. They were plastic adherent, spindle-shaped cells that expressed CD73, CD90, and CD44 but lacked CD45, CD14, HLA-DR, and CD34. cASCs differentiated toward adipogenic, osteogenic, and chondrogenic lineages, although adipogenic differentiation capacity was low. Blast transformation reaction demonstrated that these cells significantly suppress T-cell proliferation, and this ability is dose-dependent. Intravenous administration of a cell freezing medium, therapeutic dose of cASCs (2 × 106 live cells/kg), and five times higher dose of cASCs showed no significant side effects in two dogs. Microscopic tissue lesions were limited to only mild, non-specific changes. There were no signs of malignancy. The results of the study indicate that cASCs are similar to hASCs and are safe for therapeutic applications in a canine model. The proposed methodology for ASC preparation on a non-routine basis, which includes individually optimised cell culture conditions and offers risk-adapted treatment, could be used for future personalised off-the-shelf therapies, for example, in myocardial infarction or stroke.
AB - The study characterises canine adipose-derived stem cells (cASCs) in comparison to human ASCs (hASCs) and tests their safety in a canine model after intravenous administration. cASCs from two dogs were cultured under hypoxic conditions in a medium supplemented with autologous serum. They were plastic adherent, spindle-shaped cells that expressed CD73, CD90, and CD44 but lacked CD45, CD14, HLA-DR, and CD34. cASCs differentiated toward adipogenic, osteogenic, and chondrogenic lineages, although adipogenic differentiation capacity was low. Blast transformation reaction demonstrated that these cells significantly suppress T-cell proliferation, and this ability is dose-dependent. Intravenous administration of a cell freezing medium, therapeutic dose of cASCs (2 × 106 live cells/kg), and five times higher dose of cASCs showed no significant side effects in two dogs. Microscopic tissue lesions were limited to only mild, non-specific changes. There were no signs of malignancy. The results of the study indicate that cASCs are similar to hASCs and are safe for therapeutic applications in a canine model. The proposed methodology for ASC preparation on a non-routine basis, which includes individually optimised cell culture conditions and offers risk-adapted treatment, could be used for future personalised off-the-shelf therapies, for example, in myocardial infarction or stroke.
KW - advanced therapy medicinal products
KW - autologous adipose-derived stem cells
KW - hospital exemption
KW - pulmonary first-pass effect
KW - stem cell safety
UR - http://www.scopus.com/inward/record.url?scp=85045509200&partnerID=8YFLogxK
U2 - 10.2478/prolas-2018-0004
DO - 10.2478/prolas-2018-0004
M3 - Article
AN - SCOPUS:85045509200
SN - 2255-890X
VL - 72
SP - 160
EP - 171
JO - Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.
JF - Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.
IS - 3
ER -