Evidence map›Paper›PMID 40181541›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

AAV-Sparcl1 promotes hair cell regeneration by increasing supporting cell plasticity.

Nianci Li, Fangzhi Tan, Liyan Zhang, Xiaoqiong Ding, Qiuhan Sun, Man Wang, Ziyu Zhang, Yicheng Lu, Yinyi Zhou, Xiaoyun Qian and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Nianci LiDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Fangzhi TanDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.
Liyan ZhangDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Xiaoqiong DingDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Qiuhan SunDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Man WangDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Ziyu ZhangDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Yicheng LuDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Yinyi ZhouDepartment of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Xiaoyun QianDepartment of Otolaryngology-Head and Neck Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing 210008, China.
Fanglei YeDepartment of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China. Electronic address: yefanglei000@sina.com.
Jieyu QiDepartment of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; State Key Laboratory of Hearing and Balance Science, Beijing Institute of Technology, Beijing 100081, China; School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai 519088, China; Advanced Technology Research Institute, Beijing Institute of Technology, Jinan 250300, China. Electronic address: qijieyu@bit.edu.cn.
Renjie ChaiDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Department of Otolaryngology-Head and Neck Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Southeast University Shenzhen Research Institute, Shenzhen 518063, China. Electronic address: renjiec@seu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sensorineural hearing deficiency caused by hair cell damage represents a prevalent sensory deficit disorder. In mammals, age-related reduction in plasticity of inner ear supporting cells (recognized as hair cell precursors) compromises their trans-differentiation capacity, resulting in impaired spontaneous hair cell regeneration post-injury. Therapeutic reprogramming of supporting cells to functionally replace damaged hair cells has emerged as a promising strategy for sensorineural hearing loss treatment. In this study, we demonstrate that the secretory protein Sparcl1 enhances supporting cell reprogramming and hair cell regeneration in both in vitro and in vivo models. Through the adeno-associated virus (AAV)-mediated overexpression system, we successfully achieved in vivo expansion of inner ear organoids accompanied by hair cell differentiation. RNA-seq analysis revealed that Sparcl1 overexpression stimulates supporting cell proliferation via follistatin (Fst) activation and extracellular matrix (ECM) remodeling. Notably, both AAV-ie-Sparcl1 delivery and recombinant Sparcl1 protein administration effectively induced supporting cell differentiation into hair cells in vivo. Collectively, our findings establish Sparcl1 as a potent positive regulator of hair cell regeneration and elucidate mechanisms by which secretory proteins regulate supporting cell plasticity.

Indexed as

Calcium-Binding ProteinsCell PlasticityDependovirusExtracellular Matrix ProteinsGenetic VectorsHair Cells, AuditoryRegenerationAnimalsCell DifferentiationCell ProliferationDisease Models, AnimalHumansMiceCalcium-Binding ProteinsExtracellular Matrix ProteinsAAVhair cell regenerationsecretory proteinSparcl1supporting cell reprogramming

Identifiers

PMID40181541
PMCPMC12266030

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.