{"doi":"10.1101/2025.08.12.669912","title":"Functional recovery by transplantation of human iPSC-derived A2B5 positive neural progenitor cell after spinal cord injury in mice","abstract":"Human induced pluripotent stem cells (hiPSCs) hold great potential for patient-specific therapies. Transplantation of hiPSC-derived neural progenitor cells (NPCs) is a promising reparative strategy for spinal cord injury (SCI), but clinical translation requires efficient differentiation into desired neural lineages and purification before transplantation. Here, differentiated hiPSCs-reprogrammed from human skin fibroblasts using Sendai virus-mediated expression of OCT4, SOX2, KLF4, and C-MYC-into neural rosettes expressing SOX1 and PAX6, followed by neuronal precursors (β-tubulin III⁺/NESTIN⁺) and glial precursors (GFAP⁺/NESTIN⁺). Both neuronal and glial precursors expressed the A2B5 surface antigen. A2B5+ NPCs, purified by fluorescence-activated cell sorting (FACS), proliferated in vitro with mitogens and differentiated into mature neurons and astrocytes under lineage-specific conditions. NOD-SCID mice received a T9 contusion injury followed by transplantation of A2B5+ NPCs, human fibroblasts, or control medium at 8 days post-injury. At two months, grafted NPCs showed robust survival, progressive neuronal maturation (β-tubulin III⁺ → doublecortin⁺ → NeuN⁺), and astrocytic differentiation (GFAP⁺), particularly in spared white matter. Transplantation significantly increased spared white matter volume and improved hindlimb locomotor recovery, with no teratoma formation observed. These results demonstrate that hiPSC-derived, FACS-purified A2B5+ NPCs can survive, differentiate into neurons and astrocytes, and enhance functional recovery after SCI. This approach offers a safe and effective candidate cell source for treating SCI and potentially other neurological disorders.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572796,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1450005,"name":"Xiaohui Chen","orcid":"0000-0001-7672-0432","position":1,"is_corresponding":false},{"id":338273,"name":"Ping Bu","orcid":null,"position":2,"is_corresponding":false},{"id":1275852,"name":"Haipeng Xue","orcid":"0000-0002-3209-6081","position":3,"is_corresponding":false},{"id":304533,"name":"Dong Kim","orcid":"0000-0002-1523-6396","position":4,"is_corresponding":false},{"id":1397061,"name":"Hongxia Zhou","orcid":"0000-0001-9206-2580","position":5,"is_corresponding":false},{"id":1104747,"name":"Xu‐Gang Xia","orcid":null,"position":6,"is_corresponding":false},{"id":823479,"name":"Ying Liu","orcid":"0000-0003-1875-8293","position":7,"is_corresponding":false},{"id":688179,"name":"Qilin Cao","orcid":"0000-0002-3914-5325","position":8,"is_corresponding":false},{"id":688174,"name":"Yiyan Zheng","orcid":"0000-0003-1512-384X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40832190","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}