ORIGINAL RESEARCH

Cell and Organ Transplantology. 2026; 14(1):e2026141192.
DOI: 10.22494/cot.v14-1.192

Platelet-rich fibrin gel as an in situ bioreactor supporting serotonergic neuron survival and neural lineage gene expression in rat mesenchymal stem cells

Usenko O.¹, Khyzhnyak M.², Vasylieva I.², Oleksenko N.², Chopyk N.², Tsyubko N.²

• ¹Shalimov National Scientific Center of Surgery and Transplantology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
• ²Romodanov State Institute of Neurosurgery, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine

Abstract

Platelet-derived biomaterials are increasingly used in regenerative medicine as bioactive scaffolds capable of modulating cell survival, lineage-associated molecular responses, and tissue repair. Fibrin gels enriched with platelet-derived growth factors represent a promising microenvironment for neural tissue engineering, as they may support neuronal survival and promote neural lineage-associated changes in stem cells.
Objective. To evaluate the ability of a platelet-enriched fibrin gel derived from human platelet-rich plasma to function as a bioactive three-dimensional microenvironment supporting survival and morphogenesis of serotonergic neurons and neural lineage-associated changes in mesenchymal stem cells (MSCs).
Materials and methods. A platelet-enriched fibrin gel matrix was generated from platelet-rich plasma following activation with a silica-based coagulation activator. A platelet-enriched fibrin gel matrix derived from human platelet-rich plasma served as a three-dimensional culture platform for bone marrow-derived MSCs from newborn rats and for primary serotonergic cells isolated from raphe nuclei. Cultures were maintained for up to 14 days. Serotonin production was assessed using ELISA, while expression of genes associated with serotonergic phenotype maintenance (Pet1, Nkx2-2, Tph2, Slc6a4) and neural lineage-associated molecular changes (Nes, Tubb3, Gfap, Olig2) was analyzed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).
Results. Raphe-derived cells cultured within the platelet-enriched fibrin gel matrix demonstrated active neurite extension and formation of neuronal networks. Maintenance of a serotonergic phenotype was supported by histochemical detection of serotonin and by persistence of Pet1, Nkx2-2, Tph2, and Slc6a4 expression during the culture period. MSCs cultured within the matrix in the presence of neuroinductive factors (retinoic acid, NGF, and BDNF) exhibited morphological features of neural-like cells and increased expression of early neural (Nes), neuronal (Tubb3), astroglial (Gfap), and oligodendroglial (Olig2) markers compared with control cultures. These findings indicate that platelet-enriched fibrin gel functions as a bioactive three-dimensional microenvironment supporting neuronal survival and neural lineage-associated molecular changes in MSCs and may serve as an in situ bioreactor-like platform for modeling neural regeneration in vitro.
Conclusions. The platelet-enriched fibrin gel matrix provided a bioactive three-dimensional microenvironment that supported survival of serotonergic cells and modulated neural marker expression in MSCs under neuroinductive conditions. These findings are consistent with neural lineage-associated molecular responses, although additional quantitative and functional validation is required to confirm mature neural differentiation.

Keywords: platelet-enriched fibrin gel; mesenchymal stem cells; serotonergic neurons; neural lineage commitment; neural tissue engineering; regenerative medicine

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