Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)

Author(s)

Castro, Mateus Vidigal de ^[1] ; Silva, Monize Valeria Ramos da ^[1] ; Chiarotto, Gabriela Bortolanca ^{[1, 2]} ; Santana, Maria Helena Andrade ^[3] ; Luzo, Angela Cristina Malheiros ^[4] ; Kyrylenko, Sergiy ^[5] ; Oliveira, Alexandre Leite Rodrigues de ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[2] Herminio Ometto Fdn, Univ Ctr, Araras, SP - Brazil

^[3] Univ Estadual Campinas, Sch Chem Engn, Dept Engn Mat & Bioproc, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Haematol & Hemotherapy Ctr, Umbil Cord Blood Bank, Campinas, SP - Brazil

^[5] Sumy State Univ, Med Inst, Ctr Collect Use Sci Equipment, Biomat Res Grp, Sumy - Ukraine

• Document type: Journal article
• Source: STEM CELLS INTERNATIONAL; v. 2020, OCT 30 2020.
• Web of Science Citations: 0

Abstract

Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy. (AU)

• FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/26206-0 - Sensorimotor recovery after transection and spinal dorsal roots repair with platelet rich plasma (PRP) and human embryonic stem cells treatment (hESC).
• Grantee: Mateus Vidigal de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate