PMID- 38354225
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240216
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 16
IP  - 734
DP  - 2024 Feb 14
TI  - Autologous transplantation of P63(+) lung progenitor cells for chronic 
      obstructive pulmonary disease therapy.
PG  - eadi3360
LID - 10.1126/scitranslmed.adi3360 [doi]
AB  - Adult lung resident stem/progenitor cells, including P63(+) progenitor cells, 
      have demonstrated the capacity for regeneration of lung epithelium in preclinical 
      models. Here, we report a clinical trial of intrapulmonary P63(+) progenitor cell 
      transplantation in 28 participants with stage II to IV chronic obstructive 
      pulmonary disease (COPD). Autologous P63(+) progenitor cells were isolated from 
      the airway basal layer of participants in the intervention group via 
      bronchoscopic brushing, cultured for 3 to 5 weeks, and then transplanted back 
      into the lungs via bronchoscopy at 0.7 x 10(6) to 5.2 x 10(6) cells per kilogram 
      of body weight. Twenty patients were evaluable at the end of the study 
      (intervention group, n = 17; control group, n = 3). No grade 3 to 5 adverse 
      events (AEs) or serious AEs occurred. Although bronchoscopy-associated AEs were 
      recorded in participants in the intervention group, other AEs were not 
      substantial different between groups. Twenty-four weeks after transplantation, 
      participants in the intervention group displayed improvement in gas transfer 
      capacity [diffusing capacity of the lung for carbon monoxide (DLCO) change from 
      baseline: +18.2%], whereas the control group experienced a decrease (DLCO change 
      from baseline: -17.4%; P = 0.008). Furthermore, participants in the intervention 
      group showed >30-meter increase in walking distance within 6 minutes. 
      Transcriptomic analysis of progenitor cells isolated from responding and 
      nonresponding individuals in the intervention group showed that higher expression 
      of P63 was associated with treatment efficacy. In conclusion, transplantation of 
      cultured P63(+) lung progenitor cells was safe and might represent a potential 
      therapeutic strategy for COPD.
FAU - Wang, Yujia
AU  - Wang Y
AUID- ORCID: 0000-0001-9716-1115
AD  - Department of Organ Regeneration, Shanghai East Hospital, Tongji University 
      School of Medicine, Shanghai 200120, China.
FAU - Meng, Zili
AU  - Meng Z
AUID- ORCID: 0009-0001-9886-8072
AD  - Department of Respiratory and Critical Care Medicine, Affiliated Huai'an No. 1 
      People's Hospital of Nanjing Medical University, Huai'an 223300, China.
FAU - Liu, Ming
AU  - Liu M
AUID- ORCID: 0000-0001-6726-4922
AD  - State Key Laboratory of Respiratory Diseases, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 
      Medical University, Guangzhou 510120, China.
FAU - Zhou, Yueqing
AU  - Zhou Y
AUID- ORCID: 0009-0001-5180-6077
AD  - Department of Organ Regeneration, Shanghai East Hospital, Tongji University 
      School of Medicine, Shanghai 200120, China.
AD  - Super Organ R&D Center, Regend Therapeutics, Shanghai 201318, China.
FAU - Chen, Difei
AU  - Chen D
AUID- ORCID: 0000-0002-9587-6501
AD  - State Key Laboratory of Respiratory Diseases, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 
      Medical University, Guangzhou 510120, China.
FAU - Zhao, Yu
AU  - Zhao Y
AUID- ORCID: 0009-0008-7638-8853
AD  - Department of Organ Regeneration, Shanghai East Hospital, Tongji University 
      School of Medicine, Shanghai 200120, China.
FAU - Zhang, Ting
AU  - Zhang T
AUID- ORCID: 0009-0002-2427-2476
AD  - Super Organ R&D Center, Regend Therapeutics, Shanghai 201318, China.
FAU - Zhong, Nanshan
AU  - Zhong N
AUID- ORCID: 0000-0003-2274-1427
AD  - State Key Laboratory of Respiratory Diseases, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 
      Medical University, Guangzhou 510120, China.
FAU - Dai, Xiaotian
AU  - Dai X
AUID- ORCID: 0009-0003-1959-1402
AD  - Southwest Hospital, Third Military Medical University of PLA, Chongqing 400038, 
      China.
FAU - Li, Shiyue
AU  - Li S
AUID- ORCID: 0000-0001-9622-5623
AD  - State Key Laboratory of Respiratory Diseases, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 
      Medical University, Guangzhou 510120, China.
FAU - Zuo, Wei
AU  - Zuo W
AUID- ORCID: 0000-0002-4460-0337
AD  - Department of Organ Regeneration, Shanghai East Hospital, Tongji University 
      School of Medicine, Shanghai 200120, China.
AD  - Super Organ R&D Center, Regend Therapeutics, Shanghai 201318, China.
AD  - West China Hospital, Sichuan University, Chengdu 610041, China.
LA  - eng
PT  - Journal Article
DEP - 20240214
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
SB  - IM
MH  - Adult
MH  - Humans
MH  - Transplantation, Autologous
MH  - *Lung/metabolism
MH  - *Pulmonary Disease, Chronic Obstructive/metabolism
MH  - Epithelium/metabolism
MH  - Stem Cells/metabolism
EDAT- 2024/02/14 18:42
MHDA- 2024/02/16 06:42
CRDT- 2024/02/14 14:12
PHST- 2024/02/16 06:42 [medline]
PHST- 2024/02/14 18:42 [pubmed]
PHST- 2024/02/14 14:12 [entrez]
AID - 10.1126/scitranslmed.adi3360 [doi]
PST - ppublish
SO  - Sci Transl Med. 2024 Feb 14;16(734):eadi3360. doi: 10.1126/scitranslmed.adi3360. 
      Epub 2024 Feb 14.