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Here, the direction of influence of human placenta\u2010derived MSCs (P\u2010MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL\/6 mice depending on the injection method. After intramuscular co\u2010inoculation of LLC and P\u2010MSCs (LLC\u2009+\u2009P\u2010MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co\u2010cultivation of an equal amount of LLC and P\u2010MSCs. When P\u2010MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC\u2009+\u2009P\u2010MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P\u2010MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small\u2010size metastases for LLC\u2009+\u2009P\u2010MSCs(i.v.) and larger ones for LLC\u2009+\u2009P\u2010MSCs. The increase in the rate of LLC cell dissemination after the injection of P\u2010MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC\u2009+\u2009P\u2010MSCs co\u2010inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P\u2010MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P\u2010MSCs are shown to increase LLC aggressiveness related to cancer\u2010associated angiogenesis and metastasis activation in the long term.<\/jats:p>","DOI":"10.1002\/cyto.a.24814","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T12:27:43Z","timestamp":1701433663000},"page":"252-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human mesenchymal stem cells increase\n                    <scp>LLC<\/scp>\n                    metastasis and stimulate or decelerate tumor development depending on injection method and cell amount"],"prefix":"10.1002","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6349-631X","authenticated-orcid":false,"given":"Yurii V.","family":"Stepanov","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering Shenzhen University  Shenzhen People's Republic of China"},{"name":"Laboratory of Molecular and Cellular Mechanisms of Metastasis R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-6588","authenticated-orcid":false,"given":"Iuliia","family":"Golovynska","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering Shenzhen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-9099","authenticated-orcid":false,"given":"Galyna","family":"Ostrovska","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine Taras Shevchenko National University of Kyiv  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0039-7557","authenticated-orcid":false,"given":"Larysa","family":"Pylyp","sequence":"additional","affiliation":[{"name":"Clinic of Reproductive Medicine \u201cNadiya\u201d  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-6315","authenticated-orcid":false,"given":"Taisa","family":"Dovbynchuk","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine Taras Shevchenko National University of Kyiv  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-9409","authenticated-orcid":false,"given":"Liudmyla I.","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine Taras Shevchenko National University of Kyiv  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Gorbach","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Oncology National Cancer Institute of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-7947","authenticated-orcid":false,"given":"Volodymyr","family":"Shablii","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics NAS of Ukraine  Kyiv Ukraine"},{"name":"Institute of Cell Therapy  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-7746","authenticated-orcid":false,"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering Shenzhen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1527-2346","authenticated-orcid":false,"given":"Liudmyla V.","family":"Garmanchuk","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine Taras Shevchenko National University of Kyiv  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-6534","authenticated-orcid":false,"given":"Tymish Y.","family":"Ohulchanskyy","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering Shenzhen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-4711","authenticated-orcid":false,"given":"Junle","family":"Qu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering Shenzhen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8657-1263","authenticated-orcid":false,"given":"Galina I.","family":"Solyanik","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Mechanisms of Metastasis R.E. 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