Long term outcomes of intracarotid arterial transfusion of circulatory-derived autologous CD34 + cells for acute ischemic stroke patients-A randomized, open-label, controlled phase II clinical trial

Hung-Sheng Lin; Pei-Hsun Sung; Shu-Hua Huang; Wei-Che Lin; John Y Chiang; Ming-Chun Ma; Yi-Ling Chen; Kuan-Hung Chen; Fan-Yen Lee; Sheung-Fat Ko; Hon-Kan Yip

doi:10.1186/s13287-024-04021-7

Long term outcomes of intracarotid arterial transfusion of circulatory-derived autologous CD34 + cells for acute ischemic stroke patients-A randomized, open-label, controlled phase II clinical trial

Stem Cell Res Ther. 2024 Nov 20;15(1):443. doi: 10.1186/s13287-024-04021-7.

Authors

Hung-Sheng Lin¹, Pei-Hsun Sung^{2

3

4}, Shu-Hua Huang⁵, Wei-Che Lin⁶, John Y Chiang^{7

8}, Ming-Chun Ma⁹, Yi-Ling Chen^{2

3

4}, Kuan-Hung Chen¹⁰, Fan-Yen Lee¹¹, Sheung-Fat Ko¹², Hon-Kan Yip^{13

14

15

16}

Affiliations

¹ Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
² Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist., Kaohsiung City, 83301, Taiwan.
³ Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan.
⁴ Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan.
⁵ Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
⁶ Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
⁷ Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, 804201, Taiwan.
⁸ Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
⁹ Department of Internal Medicine, Division of Hema-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
¹⁰ Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
¹¹ Department of Surgery, Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
¹² Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.
¹³ Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist., Kaohsiung City, 83301, Taiwan. han.gung@msa.hinet.net.
¹⁴ Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan. han.gung@msa.hinet.net.
¹⁵ Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan. han.gung@msa.hinet.net.
¹⁶ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan. han.gung@msa.hinet.net.

PMID: 39568005
DOI: 10.1186/s13287-024-04021-7

Abstract

Background: This phase II randomized controlled trial tested whether the intracarotid arterial administration (ICAA) of autologous CD34 + cells to patients within 14 ± 7 days after acute ischemic stroke (IS) could be safe and further improve short- and long-term outcomes.

Methods: Between January 2018 and March 2022, 28 consecutive patients were equally randomly allocated to the cell-treated group (CD34 + cells/3.0 × 10⁷/patient) or the control group (receiving optimal medical therapy). CD34 + cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room.

Results: The results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all p < 0.001). Blood samples from the right internal jugular vein of the cell-treated patients presented significantly greater levels of the stromal cell-derived factor 1α/EPC at 5, 10 and 30 min compared with 0 min (all p < 0.005). The National Institute of Health Stroke Scale scores were similar upon presentation, but a greater response was observed by Days 30 and 90 in the cell-treated group than in the control group. Tc-99 m brain perfusion was significantly greater at 180 days in the cell-treated group than in the control group (p = 0.046). The combined long-term end points (defined as death/recurrent stroke/or severe disability) were notably lower in the control group compared with the cell-treated group (14.3% vs. 50.0%, p = 0.103).

Conclusion: Intracarotid transfusion of autologous CD34 + cells is safe and might improve long-term outcomes in patients with acute IS. Trial registration ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, https://doi.org/10.1186/ISRCTN15677760.

Keywords: Acute ischemic stroke; Angiogenesis; Endothelial progenitor cells; Intracarotid transfusion of CD34 + cells; Neurological outcomes.

Associated data

ISRCTN/ISRCTN15677760

Grants and funding

MOST 107-2314-B-182A-056-MY3/Ministry of Science and Technology of the Republic of China