Peripheral nerve injury (PNI) is a common type of nervous system damage, characterized by significant impairments in motor function, sensitivity and chronic pain (Houdek, Shin, 2015; Bateman et al., 2024). Although the incidence of PNI is relatively low in peacetime (Melikov, Medvediev, 2024; Zaidman et al., 2024), it increases significantly during military conflicts (Tsymbaliuk et al., 2015, 2021), where this type of injury is often combined with vascular and limb bone damage (Muss et al., 2024), significantly worsening treatment outcomes (Tsymbaliuk et al., 2015, 2021; Strafun et al., 2018).
Given the age, sex, and topographic-anatomical specificity of PNI (Bergmeister et al., 2020; Zaidman et al., 2024), its surgical treatment, and the need for prolonged rehabilitation (Bateman et al., 2024; Zaidman et al., 2024), this pathology is financially costly (Bergmeister et al., 2020; Raizman et al., 2023).
Despite the significant regenerative potential of the nervous system and advancements in PNI treatment, its effectiveness remains limited (Tsymbaliuk et al., 2020; Melikov, Medvediev, 2023). This is due to the lack of satisfactory conditions for nerve fibers growth across the injury site (Harley-Troxell et al., 2023), secondary neuronal death (Liu, Wang, 2020; Pottorf et al., 2022), restricted plasticity of neural networks (Li et al., 2021; Shen, 2022) and the rapid atrophy of denervated muscles (Goncharuk et al., 2021, 2023; Lysak et al., 2024).
The survival of neurons, damaged during PNI and the plasticity of neural networks in the brain may be enhanced by mesenchymal stem cells (MSCs) transplanted into the cerebrospinal fluid. MSCs are a type of stromal stem cell capable of producing a wide range of supportive and pro-neuroplastic factors (Han et al., 2022; Kou et al., 2022; Lopes et al., 2022).
This type of regenerative treatment for PNI remains insufficiently studied (Melikov, Medvediev, 2023; Melikov et al., 2025), which served as the motivation for this dissertation research.
Experimental Design. Animals — male outbred white rats (4–6 months old, 280– 380 g of weigh). Experimental groups: Sham — sham-operated group with surgical exposure of the sciatic nerve (n=32); Sect — sciatic nerve transection (n=33); Raph — sciatic nerve transection + immediate nerve suturing (n=32); Phys — sciatic nerve transection + immediate nerve suturing + intrathecal administration of physiological saline at 13–15 days post-injury (n=31); DrSC — sciatic nerve transection + immediate nerve suturing + intrathecal administration of a suspension of multipotent stromal stem cells derived from adult human skin at 13–15 days post-injury (n=15); MSC-UA — sciatic nerve transection + immediate nerve suturing + intrathecal administration of a suspension of mesenchymal stem cells derived from the human umbilical artery at 13– 15 days post-injury (n=16). Observation period — up to 24 weeks post-primary intervention for all groups. Gradual animal euthanasia for electrophysiological and morphological studies: Sham, Sect, Raph, and Phys groups — at 4, 8, 12, and 24 weeks; DrSC and MSC-UA groups — at 24 weeks. Stem cell sources: human umbilical artery (n=2) and adult human skin samples from both sexes, obtained via punch-biopsy (n=2). Stem cell processing algorithm: primary isolation, initial culture and expansion, immunophenotyping of the culture, assessment of osteogenic and adipogenic differentiation, cryopreservation, thawing and further expansion to the required quantity. Route of transplantation: intrathecal administration into the subarachnoid space, specifically into the cisterna magna, performed under deep anesthesia.
