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This article belongs to the Topic Emerging Translational Research in Neurological and Psychiatric Diseases: from In Vitro to In Vivo Models., From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development., DM research is funded by Croatian Science Foundation project Orastem (IP-16-6-9451) and by European Union through the European Regional Development Fund, as the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience under Grant Agreement No. KK.01.1.1.01.0007, project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain”. VH and DJ are supported by PhD grants by Croatian Science Foundation. LM research is partly funded by the AGING Project for Department of Excellence at the Department of Translational Medicine (DIMET), Università del Piemonte Orientale, Novara, Italy. LR and JM research is supported by Grants no 451-03-68/2020-14/200178 and no 451-03-9/2021-14/200129 of the Ministry of Education, Science and Technological Development of Republic of Serbia. GF was supported by Medical Research Council [MR/R025002/1], NIHR Imperial Biomedical Research Centre and the Hungarian National Research, Development and Innovation Fund [2020-1.1.6-JÖVŐ-2021-00013 and K128369]. A.H, F.L., A.D were supported by EU Horizon 2020 Marie Skłodowska-Curie grant agreement No 812660 (DohART-NET) and Grant Agreement No. 739593 (HCEMM) (for A.D) and Chinese-Hungarian Bilateral Project (2018-2.1.14-TÉT-CN-2018-00011, Chinese No. 8-4 (for A.D.) SM is founded by Spanish State Research Agency SAF2017-83702-R and the TERCEL (Instituto de Salud Carlos III (RD16/001/0010 and PID2020-11817RB-100). LB is supported by National Science Centre, Poland, grant # 2019/35/B/NZ3/04383.