RGTA®-based matrix therapy - A new branch of regenerative medicine in locomotion.
Matrix therapy is an innovative, minimally invasive approach in the field of regenerative medicine, that aims to promote tissue regeneration by reconstructing the cellular microenvironment following tissue injury. This approach has significant therapeutic potential in the treatment of pathologies characterized by tissue inflammation and damage, or following injury, conditions which can be incapacitating and cost-consuming. Heparan sulfate mimics, termed ReGeneraTing Agents (RGTA®s) have emerged as a unifying approach to treat these diverse pathologies. Today, skin and corneal healing topical products have already been used in clinics, demonstrating a proof of concept in humans. In this review, we present key evidence that RGTA®s regenerate damaged tissue in bone, muscle, tendon and nerve, with astonishing results. In animal models of bone surgical defects and inflammatory bone loss, RGTA®induced healing of injured bones by controlling inflammation and bone resorption, and stimulated bone formation by coordinating vascularization, recruitment and differentiation of competent cells from specific niches, restoring tissue quality to that of uninjured tissue, evoking true regeneration. In models of muscle injury, RGTA®had marked effects on healing speed and quality, evidenced by increased muscle fiber density, maturation, vascularization and reduced fibrosis, more mature motor endplates and functional recovery. Applications merging RGTA®-based matrix therapy and cell therapy, combining Extra-Cellular Matrix reconstruction with cells required for optimal tissue repair show significant promise. Hence restoration of the proper microenvironment is a new paradigm in regenerative medicine. Harnessing the potential of RGTA®in this brave, new vision of regenerative therapy will therefore be the focus of future studies.
Université Paris-Est Créteil, Laboratoire CRRET and OTR3, 4 rue Française, 75001 Paris, 1.2, France. Electronic address: denis.barritault@otr3.com.
Denis
D
Barritault
Université Paris-Est-Créteil, Hôpital Henri Mondor, Paris XII, Vascular Surgery Unit, 51, av du MI de Lattre de Tassigny, 94010 Creteil, France.
Pascal
P
Desgranges
Inserm U1148, LVTS, Université Paris 7, Université Paris 13, Sorbonne Paris Cité, Hôpital Bichat, 46 rue H Huchard, 75018 Paris, France.
Anne
A
Meddahi-Pellé
Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, USC 957 BPLC, 94700 Maisons-Alfort, France; Centre d'Imagerie et de Recherche sur les Affections Locomotrices Equine (CIRALE), 14430 Goustranville, France.
Jean-Marie
JM
Denoix
EA2496 Laboratoire Pathologies, Imagerie et Biothérapies Oro-Faciales, Faculté de Chirurgie Dentaire, Université Paris Descartes, Sorbonne Paris Cité, 1 rue Maurice Arnoux, 92120 Montrouge, France.
Jean-Louis
JL
Saffar
D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005109:Extracellular Matrix; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008124:Locomotion; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D054457:Tissue Scaffolds
D006493:Heparin
Bone healing; Extracellular scaffold; Heparan sulfate mimics; Ischemia; Osteoblasts; RGTA(®); Regeneration; Revascularization; Tendon