The human dental apical papilla promotes spinal cord repair through a paracrine mechanism

• Published in: Cellular and molecular life sciences : CMLS 2022-05, Vol.79 (5), p.252-252, Article 252
• Main Authors: De Berdt, P., Vanvarenberg, K., Ucakar, B., Bouzin, C., Paquot, A., Gratpain, V., Loriot, A., Payen, V., Bearzatto, B., Muccioli, G. G., Gatto, L., Diogenes, A., des Rieux, A.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell survival; Cytokines; Female; Humans; Immunohistochemistry; Immunomodulation; Injury prevention; Lesions; Life Sciences; Macrophages; Microglia; Motor neurons; Neuroprotection; Original; Original Article; Paracrine signalling; Protein arrays; Rats; Recovery of function; Repair; Secretome; Spinal Cord - metabolism; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - therapy; Spinal Cord Regeneration; Stem cell transplantation; Stem Cells; Transplantation
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-022-04210-8

Traumatic spinal cord injury is an overwhelming condition that strongly and suddenly impacts the patient’s life and her/his entourage. There are currently no predictable treatments to repair the spinal cord, while many strategies are proposed and evaluated by researchers throughout the world. One of the most promising avenues is the transplantation of stem cells, although its therapeutic efficiency is limited by several factors, among which cell survival at the lesion site. In our previous study, we showed that the implantation of a human dental apical papilla, residence of stem cells of the apical papilla (SCAP), supported functional recovery in a rat model of spinal cord hemisection. In this study, we employed protein multiplex, immunohistochemistry, cytokine arrays, RT- qPCR, and RNAseq technology to decipher the mechanism by which the dental papilla promotes repair of the injured spinal cord. We found that the apical papilla reduced inflammation at the lesion site, had a neuroprotective effect on motoneurons, and increased the apoptosis of activated macrophages/ microglia. This therapeutic effect is likely driven by the secretome of the implanted papilla since it is known to secrete an entourage of immunomodulatory or pro-angiogenic factors. Therefore, we hypothesize that the secreted molecules were mainly produced by SCAP, and that by anchoring and protecting them, the human papilla provides a protective niche ensuring that SCAP could exert their therapeutic actions. Therapeutic abilities of the papilla were demonstrated in the scope of spinal cord injury but could very well be beneficial to other types of tissue.