HPMA-RGD Hydrogels Seeded with Mesenchymal Stem Cells Improve Functional Outcome in Chronic Spinal Cord Injury

Abstract

Chronic spinal cord injury (SCI) is characterized by tissue loss and a stable functional deficit. While several experimental therapies have proven to be partly successful for the treatment of acute SCI, treatment of chronic SCI is still challenging. We studied whether we can bridge a chronic spinal cord lesion by implantation of our newly developed hydrogel based on 2-hydroxypropyl methacrylamide, either alone or seeded with mesenchymal stem cells (MSCs), and whether this treatment leads to functional improvement. A balloon-induced compression lesion was performed in adult 2-month-old male Wistar rats. Five weeks after injury, HPMA-RGD hydrogels [N-(2-hydroxypropyl)-methacrylamide with attached amino acid sequences--Arg-Gly-Asp] were implanted into the lesion, either with or without seeded MSCs. Animals with chronic SCI served as controls. The animals were behaviorally tested using the Basso–Beattie-Breshnahan (BBB) (motor) and plantar (sensory) tests once a week for 6 months. Behavioral analysis showed a statistically significant improvement in rats with combined treatment, hydrogel and MSCs, compared with the control group (P < 0.05). Although a tendency toward improvement was found in rats treated with hydrogel only, this was not significant. Subsequently, the animals were sacrificed 6 months after SCI, and the spinal cord lesions evaluated histologically. The combined therapy (hydrogel with MSCs) prevented tissue atrophy (P < 0.05), and the hydrogels were infiltrated with axons myelinated with Schwann cells. Blood vessels and astrocytes also grew inside the implant. MSCs were present in the hydrogels even 5 months after implantation. We conclude that 5 weeks after injury, HPMA-RGD hydrogels seeded with MSCs can successfully bridge a spinal cord cavity and provide a scaffold for tissue regeneration. This treatment leads to functional improvement even in chronic SCI.

Pluripotent Stem Cells and Their Dynamic Niche

“…In summary, the capacity of MSC to change their default state and their potential to promote tissue regeneration may surpass their application for haematopoietic diseases and might make them a suitable tool to treat degenerative diseases such as neurological and neurodegenerative disorders [154]. Employing MSC in combination with biomaterials or alone resulted in functional regeneration of paralysed limbs, diminished cavity formation in the spinal cord and axonal regrowth [155][156][157][158]. MSCs have also been utilised in first clinical trials to treat myocardial infarcts, stroke and diseases of the CNS [159,160].…”

The collagen scaffold with collagen binding BDNF enhances functional recovery by facilitating peripheral nerve infiltrating and ingrowth in canine complete spinal cord transection

“…[13][14][15] To further investigate whether peripheral nerve infiltrating into CSCB implant, we checked Schwann cells infiltrating by S-100 (Schwann cells' marker) immunochemistry staining. In the center of damaged spinal cord, S-100 staining showed similar pattern with NF-staining and it implied Schwann cells infiltrated into CSCB implant ( Figure 5).…”

Hydrogels in Spinal Cord Injury Repair Strategies

“…Stem cells are mainly chosen between multipotent cell lines (mesenchymal and neural) 99,103À107 and pluripotent ones (embryonic). 108 Synthetic materials that seem to be extremely suitable as 3D growth matrices are polymethacrylates, such as pHPMA and pHEMA, which were tested with mesenchymal stem cells 103 and also showed relevant improvement in chronic spinal cord injury. 103,109,110 In addition some studies, involving polymethacylates, underlined relevant functional improvements on animals after hydrogel implantation: pHEMA and pHPMA favor axonal ingrowth, 111 showing also good outcome in chronic cases as said before, 103 while pHEMA-MMA influences axonal regrowth.…”