Spinal cord tissue engineering using human primary neural progenitor cells and astrocytes

Abstract

Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter‐scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord‐like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.

Mimicked Spinal Cord Fibers Trigger Axonal Regeneration and Remyelination after Injury

“…Aligned structural scaffolds have been extensively studied for spinal nerve regeneration, since they are known to facilitate the directed growth of axons. , Aligned fibrin or aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel enhanced axonal regeneration compared to hollow conduits, and aligned collagen/fibrin hydrogel nanofibers loaded with SDF1α promoted the directed migration and differentiation of endogenous stem cells . Our previous studies demonstrated axons extending directionally on linearly ordered collagen scaffold (LOCS) like axons in centimeter-scale human spinal cord neural tissue constructed by human spinal cord neural progenitor cells and human spinal cord astrocyte were arranged in LOCS orderly . In this study, a series of physical, chemical, and enzymatic treatments were used to remove cellular components from porcine spinal cord tissues.…”

“…Female SD rats weighing 220−250 g were completely traversed about 3 mm at the thoracic 8−10 segment according to our previous study. 49 They were randomly divided into five groups (10 rats/ group): SCI, A-CF, A-DSCF, A-CF/NPC (loaded with a total of 1 × 10 6 GFP + cells per scaffold), and A-DSCF/NPC (loaded with a total of 1 × 10 6 GFP + cells per scaffold). After the surgery, the rats were given penicillin streptomycin and glucose for 1 week, and their bladders were manually squeezed twice a day to facilitate urine elimination until the restoration of urinary reflex.…”

“…The handling procedures followed the “Guidelines for the Care and Use of Laboratory Animals”, which has approved by the Ethics Committee of the Institute of Genetics and Developmental Biology (AP2020004), Chinese Academy of Sciences. Female SD rats weighing 220–250 g were completely traversed about 3 mm at the thoracic 8–10 segment according to our previous study . They were randomly divided into five groups (10 rats/group): SCI, A-CF, A-DSCF, A-CF/NPC (loaded with a total of 1 × 10 6 GFP + cells per scaffold), and A-DSCF/NPC (loaded with a total of 1 × 10 6 GFP + cells per scaffold).…”

“…48 Our previous studies demonstrated axons extending directionally on linearly ordered collagen scaffold (LOCS) like axons in centimeter-scale human spinal cord neural tissue constructed by human spinal cord neural progenitor cells and human spinal cord astrocyte were arranged in LOCS orderly. 49 In this study, a series of physical, chemical, and enzymatic treatments were used to remove cellular components from porcine spinal cord tissues. The spinal cord (SC) and decellularized spinal cord matrix (DSCM) were characterized by hematoxylin and eosin (H&E) staining and DNA content analysis (Figure 2B, C).…”

Collagen for neural tissue engineering: Materials, strategies, and challenges

“…Researchers have fabricated novel centimetre-scale human spinal cord neural tissue constructs with human spinal cord NPCs and astrocytes combined with a linearly ordered collagen scaffold. In this case, astrocytes could facilitate NPC adhesion and neurite outgrowth on the collagen scaffold, forming a linearly ordered spinal cord-like structure comprising mature neurons and glia cells [ 212 ].…”