Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury

Abstract

Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.

A 3D‐Printed Dual Driving Forces Scaffold with Self‐Promoted Cell Absorption for Spinal Cord Injury Repair

“…While many studies implemented graft 2 weeks post‐injury due to the toxic and inflammatory environment at acute lesion sites, scaffolds could protect and support grafted cells survival in acute SCI. [ 3,13 ]…”

“…The need to improve the efficiency of the tedious cell seeding and cell-loading on scaffolds has been recognized. [3,15] To determine whether HES improves the efficiency of cell seeding, we recorded the entire process of seeding of hAESCs onto the HES. Figure 4a vividly showed all items used in this process, including sterile packaged HES and hAESCs.…”

“…[1,2] The main contributors to poor recovery from SCI are a nonpermissive microenvironment and insufficient replenishment of cells in the lesion. [3,4] To date, no safe and effective clinical therapy could strike a balance between inhibiting neuroinflammation and restoring neural circuits after SCI. [5][6][7] Over the last decade, significant progress has been made toward elucidating the molecular and cellular mechanisms governing SCI pathology, as well as understanding the limitations of reparative strategies relying solely on biomaterials or stem cell transplantation.…”

“…HES functions in a similar way to a vacuum cleaner by efficiently absorbing hAESCs driven by dual driving forces. Scaffolds volume: a 50-60 mm 3 GelMA scaffold is designed and printed; After SAA postprocessing, the scaffold shrinks to ≈1 mm 3 and can be packaged independently; After rehydration in cell suspension, the volume of HES-hAESCs returns back to ≈50 mm 3 . Abbreviations: SCI, spinal cord injury; TPMS, three-period minimal surface; GelMA, gelatin-methacryloyl; SAA, super absorption and attachment; HES, hyper expansion scaffold; hAESCs, human amniotic epithelial stem cells; HES-hAESCs, high hAESCs-loaded HES.…”

Stem Cell- and Cell-Based Therapies for Ischemic Stroke

“…A solution to this problem might be the obtaining of iPSC-derived NSCs [ 110 ]. In addition, grafting of the stem cells embedded in scaffolds, such as 3D-printed hydrogel scaffolds, increases their survival rate and enables their migration to lesion sites [ 111 ].…”