Journal Home > Volume 11 , Issue 2
Journal of Neurorestoratology 2023, 11(2): 100052 https://doi.org/10.1016/j.jnrt.2023.100052
Protocol | Open Access | Issue | Published: 14 April 2023

Clinical trial of intrathecal injection of protein polymers for apoplexy: A protocol

Show Author's Information Lu Diaoa,1,  Xiaoyan Liua,1,  Mingze Chaia,1,  Jianjun Lib,1,  Yu Wangb,  Wenyong Gaob,  Haisheng Liuc( ),  Mi Liua( ),  Lin Chenb,d( )
Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, Jiangsu China
Beijing Darwin Cell Biotechnology Co., Ltd., Beijing 100043, China
Shouyi Chinese Medicine Hospital, Beijing 100043, China
Department of Neurosurgery, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100007, China

1 These authors contributed equally to this work.

Keywords:
Ischemic stroke, Mesenchymal stem cells, Clinical trial, Apoplexy, Human umbilical cord mesenchymal stem cells, Protein polymer
Cite this article:
Diao L, Liu X, Chai M, et al. Clinical trial of intrathecal injection of protein polymers for apoplexy: A protocol. Journal of Neurorestoratology, 2023, 11(2): 100052. https://doi.org/10.1016/j.jnrt.2023.100052
Download citation
EndNote(RIS)
BibTeX

321

Views

28

Downloads

Citations

0

Crossref

0

WoS

0

Scopus

N/A

CSCD

Abstract Full text About this article

Protein polymers derived from mesenchymal stem cells, especially human umbilical cord mesenchymal stem cells, showed promising potentials in treating ischemic stroke, thanks to the advantages of selective assembly, targeted delivery, efficient repair of damaged tissues, high safety, highly stable chemical properties, and being easy for storage. Herein, we introduced a clinical trial based on protein polymers derived from human umbilical cord mesenchymal stem cells. The main purpose of this clinical study is to preliminarily verify the safety and efficacy of intrathecal administration and application of protein polymers in clinical treatment of ischemic stroke cases. The summary of the program, the research plan, test protein polymer intrathecal injection method, experimental protein polymer management, patient evaluation index, data management and statistical analysis, technical features, trial schedule etc. are detailed described in the article. This clinical study provides information for other clinical trials based on protein polymers and medicines used to treat apoplexy.


menu
Abstract
Full text
Outline
About this article

Clinical trial of intrathecal injection of protein polymers for apoplexy: A protocol

Show Author's information Lu Diaoa,1, Xiaoyan Liua,1, Mingze Chaia,1, Jianjun Lib,1, Yu Wangb, Wenyong Gaob, Haisheng Liuc( ), Mi Liua( ), Lin Chenb,d( )
Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, Jiangsu China
Beijing Darwin Cell Biotechnology Co., Ltd., Beijing 100043, China
Shouyi Chinese Medicine Hospital, Beijing 100043, China
Department of Neurosurgery, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100007, China

1 These authors contributed equally to this work.

Abstract

Protein polymers derived from mesenchymal stem cells, especially human umbilical cord mesenchymal stem cells, showed promising potentials in treating ischemic stroke, thanks to the advantages of selective assembly, targeted delivery, efficient repair of damaged tissues, high safety, highly stable chemical properties, and being easy for storage. Herein, we introduced a clinical trial based on protein polymers derived from human umbilical cord mesenchymal stem cells. The main purpose of this clinical study is to preliminarily verify the safety and efficacy of intrathecal administration and application of protein polymers in clinical treatment of ischemic stroke cases. The summary of the program, the research plan, test protein polymer intrathecal injection method, experimental protein polymer management, patient evaluation index, data management and statistical analysis, technical features, trial schedule etc. are detailed described in the article. This clinical study provides information for other clinical trials based on protein polymers and medicines used to treat apoplexy.

Keywords: Ischemic stroke, Mesenchymal stem cells, Clinical trial, Apoplexy, Human umbilical cord mesenchymal stem cells, Protein polymer

References(49)

1

Muthukumar N. Pituitary apoplexy: a comprehensive review. Neurol India. 2020;68(suppl ment):S72-S78.
Google Scholar
2

Serramito-García R, García-Allut A, Arcos-Algaba AN, et al. Pituitary apoplexy. A review (in Spanish). Neurocirugia. 2011;22(1):44-49.
DOI Google Scholar
3

Jiang QH, Xiao S, Shu LM, et al. Pituitary apoplexy leading to cerebral infarction: a systematic review. Eur Neurol. 2020;83(2):121-130.
DOI Google Scholar
4

Picón Jaimes YA, Orozco Chinome JE, López Cepeda D, et al. Pituitary apoplexy in pediatric patients: systematic review (in Spanish). Rev Fac Cien Med Univ Nac Cordoba. 2022;79(2):141-145.
DOI Google Scholar
5

Elarjani T, Chen S, Cajigas I, et al. Pituitary apoplexy and cerebral infarction: case report and literature review. World Neurosurg. 2020;141:73-80.
DOI Google Scholar
6

Majovsky M, Netuka D, Lipina R, et al. Pineal apoplexy: a case series and review of the literature. J Neurol Surg Cent Eur Neurosurg. 2022;83(1):31-38.
DOI Google Scholar
7

Hu BL, Chen SF, Zou M, et al. Effect of extracellular vesicles on neural functional recovery and immunologic suppression after rat cerebral apoplexy. Cell Physiol Biochem. 2016;40(1/2):155-162.
DOI Google Scholar
8

Hashimoto G, Wada S, Yoshino F, et al. Case report: transient ischemic stroke caused by internal carotid artery occlusion due to compression by pituitary apoplexy and hemodynamic mechanism (in Japanese). Rinsho Shinkeigaku. 2020;60(2):146-151.
DOI Google Scholar
9

Ahn JM, Oh HJ, Oh JS, et al. Pituitary apoplexy causing acute ischemic stroke: which treatment should be given priority. Surg Neurol Int. 2020;11:113.
DOI Google Scholar
10

Hoang DM, Pham PT, Bach TQ, et al. Stem cell-based therapy for human diseases. Signal Transduct Targeted Ther. 2022;7(1):272.
DOI Google Scholar
11

Li YC, Zhong W, Tang XQ. Strategies to improve the efficiency of transplantation with mesenchymal stem cells for the treatment of ischemic stroke: a review of recent progress. Stem Cell Int. 2021;2021, 9929128.
DOI Google Scholar
12

Chen HL, Cai YH, Sun SJ, et al. Repair effect of photobiomodulation combined with human umbilical cord mesenchymal stem cells on rats with acute lung injury. J Photochem Photobiol, B. 2022;234:112541.
DOI Google Scholar
13

Roever L, Jickling GC. Mesenchymal stem cells for ischemic stroke: hope or hype? Neurology. 2021;96(7):301-302.
DOI Google Scholar
14

Lee J, Chang WH, Chung JW, et al. Efficacy of intravenous mesenchymal stem cells for motor recovery after ischemic stroke: a neuroimaging study. Stroke. 2022;53(1):20-28.
DOI Google Scholar
15

Ikegame Y. Among mesenchymal stem cells: for the best therapy after ischemic stroke. Stem Cell Res Ther. 2013;4(1):9.
DOI Google Scholar
16

Ikegame Y, Yamashita K, Hayashi SI, et al. Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy. 2011;13(6):675-685.
DOI Google Scholar
17

Gutiérrez-Fernández M, Rodríguez-Frutos B, Álvarez-Grech J, et al. Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. Neuroscience. 2011;175:394-405.
DOI Google Scholar
18

Li WY, Choi YJ, Lee PH, et al. Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant. 2008;17(9):1045-1059.
DOI Google Scholar
19

Diekhorst L, Frutos MCGD, Laso-García F, et al. Mesenchymal stem cells from adipose tissue do not improve functional recovery after ischemic stroke in hypertensive rats. Stroke. 2020;51(1):342-346.
DOI Google Scholar
20

Doeppner TR, Hermann DM. Mesenchymal stem cells in the treatment of ischemic stroke: progress and possibilities. Stem Cells Clon. 2010;3:157-163.
DOI Google Scholar
21

Hill AJ, Zwart I, Tam HH, et al. Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats. Stem Cell Dev. 2009;18(3):399-409.
DOI Google Scholar
22

Liu FB, Lin Q, Liu ZW. A study on the role of apoptotic human umbilical cord mesenchymal stem cells in bleomycin-induced acute lung injury in rat models. Eur Rev Med Pharmacol Sci. 2016;20(5):969-982.
Google Scholar
23

Wang LM, Tran I, Seshareddy K, et al. A comparison of human bone marrow-derived mesenchymal stem cells and human umbilical cord-derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Eng. 2009;15(8):2259-2266.
DOI Google Scholar
24

Huang JR, Li Q, Yuan XH, et al. Intrauterine infusion of clinically graded human umbilical cord-derived mesenchymal stem cells for the treatment of poor healing after uterine injury: a phase Ⅰ clinical trial. Stem Cell Res Ther. 2022;13(1):85.
DOI Google Scholar
25

Yang DW, Lin HM, Liu GP. Immunogenicity of human umbilical cord blood derived mesenchymal stem cells after osteogenic induction (in Chinese). Chin J Reparative Reconstr Surg. 2014;28(6):752-757.
Google Scholar
26

Lee M, Jeong SY, Ha J, et al. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun. 2014;446(4):983-989.
DOI Google Scholar
27

Yang XF, Chen T, Ren LW, et al. Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells. Exp Ther Med. 2017;13(4):1456-1464.
DOI Google Scholar
28

Wang P, Liu X, Zhao L, et al. Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium. Acta Biomater. 2015;18:236-248.
DOI Google Scholar
29

Zhang S, Zhang WW, Li YP, et al. Human umbilical cord mesenchymal stem cell differentiation into odontoblast-like cells and endothelial cells: a potential cell source for dental pulp tissue engineering. Front Physiol. 2020;11:593.
DOI Google Scholar
30

Diao YZ, Ma QJ, Cui FZ, et al. Human umbilical cord mesenchymal stem cells: osteogenesis in vivo as seed cells for bone tissue engineering. J Biomed Mater Res. 2009;91(1):123-131.
DOI Google Scholar
31

Pan YQ, Jiao GL, Yang JG, et al. Insights into the therapeutic potential of heparinized collagen scaffolds loading human umbilical cord mesenchymal stem cells and nerve growth factor for the repair of recurrent laryngeal nerve injury. Tissue Eng Regen Med. 2017;14(3):317-326.
DOI Google Scholar
32

Qian C, Zhang ZQ, Zhao R, et al. Effect of acellular nerve scaffold containing human umbilical cord-derived mesenchymal stem cells on nerve repair and regeneration in rats with sciatic nerve defect. Ann Transl Med. 2022;10(8):483.
DOI Google Scholar
33

Guo ZY, Sun X, Xu XL, et al. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms. Neural Regen Res. 2015;10(4):651-658.
DOI Google Scholar
34

Zhai LL, Maimaitiming Z, Cao X, et al. Nitrogen-doped carbon nanocages and human umbilical cord mesenchymal stem cells cooperatively inhibit neuroinflammation and protect against ischemic stroke. Neurosci Lett. 2019;708:134346.
DOI Google Scholar
35

Li YC, Hu GH, Cheng QL. Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges. Front Med. 2015;9(1):20-29.
DOI Google Scholar
36

Cao HL, Zhu XF, Zhang J, et al. Dose-dependent effects of tetramethylpyrazine on the characteristics of human umbilical cord mesenchymal stem cells for stroke therapy. Neurosci Lett. 2020;722:134797.
DOI Google Scholar
37

Tanaka E, Ogawa Y, Mukai T, et al. Dose-dependent effect of intravenous administration of human umbilical cord-derived mesenchymal stem cells in neonatal stroke mice. Front Neurol. 2018;9:133.
DOI Google Scholar
38

Zhu H, Xiong Y, Xia YQ, et al. Therapeutic effects of human umbilical cord-derived mesenchymal stem cells in acute lung injury mice. Sci Rep. 2017;7:39889.
DOI Google Scholar
39

Xiong N, Zhang Z, Huang J, et al. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease. Gene Ther. 2011;18(4):394-402.
DOI Google Scholar
40

Li JF, Wang YL, Liu XS, et al. Therapeutic effects of CUR-activated human umbilical cord mesenchymal stem cells on 1-methyl-4-phenylpyridine-induced Parkinson's disease cell model. BioMed Res Int. 2016;2016, 9140541.
DOI Google Scholar
41

Editors PO. Retraction: conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopamine neurons mediated by the Lmx1a and Neurturin in Vitro: potential therapeutic application for Parkinson's disease in a rhesus monkey model. PLoS One. 2020;15(11), e0242032.
DOI Google Scholar
42

Sun Z, Gu P, Xu H, et al. Human umbilical cord mesenchymal stem cells improve locomotor function in Parkinson's disease mouse model through regulating intestinal microorganisms. Front Cell Dev Biol. 2022;9:808905.
DOI Google Scholar
43

Liu KZ, Veenendaal T, Wiendels M, et al. Synthetic extracellular matrices as a toolbox to tune stem cell secretome. ACS Appl Mater Interfaces. 2020;12(51):56723-56730.
DOI Google Scholar
44

Chen JM, Chin A, Almarza AJ, et al. Hydrogel to guide chondrogenesis versus osteogenesis of mesenchymal stem cells for fabrication of cartilaginous tissues. Biomed Mater. 2020;15(4), 045006.
DOI Google Scholar
45

Ganesh A, Barber P, Black SE, et al. Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol. BMJ Open. 2020;10(10), e040466.
DOI Google Scholar
46

Yang YM, Zhao ZM, Wang W, et al. Trends in cognitive function assessed by a battery of neuropsychological tests after mild acute ischemic stroke. J Stroke Cerebrovasc Dis. 2020;29(7):104887.
DOI Google Scholar
47

Chabriat H, Bassetti CL, Marx U, et al. Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2020;19(3):226-233.
DOI Google Scholar
48

Xu W, Jin W, Zhang XX, et al. Remote limb preconditioning generates a neuroprotective effect by modulating the extrinsic apoptotic pathway and TRAIL-receptors expression. Cell Mol Neurobiol. 2017;37(1):169-182.
DOI Google Scholar
49

Cappellari M, Forlivesi S, Zucchella C, et al. Factors influencing cognitive performance after 1-year treatment with direct oral anticoagulant in patients with atrial fibrillation and previous ischemic stroke: a pilot study. J Thromb Thrombolysis. 2021;51(3):767-778.
DOI Google Scholar
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 19 September 2022
Revised: 18 January 2023
Accepted: 31 January 2023
Published: 14 April 2023
Issue date: June 2023

Copyright

© 2023 The Authors.

Acknowledgements

Acknowledgements

The study is supported by Beijing Darwin Cell Biotechnology Co., Ltd., Beijing, China.

Rights and permissions

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Return