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LU Xiao, WANG Xingru, QI Xueyong, et al. Research progress and existing problems in the industrialization of stem cell drugs[J]. J China Pharm Univ, 2024, 55(2): 270 − 280. DOI: 10.11665/j.issn.1000-5048.2023111604
Citation: LU Xiao, WANG Xingru, QI Xueyong, et al. Research progress and existing problems in the industrialization of stem cell drugs[J]. J China Pharm Univ, 2024, 55(2): 270 − 280. DOI: 10.11665/j.issn.1000-5048.2023111604

Research progress and existing problems in the industrialization of stem cell drugs

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  • Received Date: November 15, 2023
  • Stem cells, which are a type of primitive cells with multipotent differentiation potential and self-renewal ability, have the potential to regenerate various tissues and organs. Stem cell drug development is a frontier research field in life sciences. Extensive clinical trials involving stem cells have been conducted for different complicated diseases. Some stem cells have been approved as drugs for some indications, indicating their broad industrial prospects. This review introduces the progress of stem cell drugs around the world, especially in China, and discusses the main problems in the industrialization of stem cell drugs, such as their effectiveness, quality control and safety, so as to provide some reference and insight for the development and rapid industrialization of stem cell drugs.

  • [1]
    Yuan BZ. The Law-Regulation-Guidance regulatory system for stem cell-based medicinal products[J]. Chin Bull Life Sci (生命科学), 2016, 28(8): 949-957.
    [2]
    Cheng HY, Chang XH, Liu CX, et al. Current status and future of stem cell clinical research and management[J]. Drug Eval Res (药物评价研究), 2021, 44(2): 243-249.
    [3]
    Wang J, Huang YH, Gao CY. Current application and registration status of mesenchymal stem cell products and considerations on its clinical review[J]. Chin J N Drugs (中国新药杂志), 2022, 31(15): 1468-1473.
    [4]
    Gao JC, Wei W, Zhang M, et al. Progress and prospect of regulatory science in cell and gene therapy products[J]. Chin J N Drugs (中国新药杂志), 2022, 31(2): 105-108.
    [5]
    Dorronsoro A, Ferrin I, Salcedo JM, et al. Human mesenchymal stromal cells modulate T-cell responses through TNF-α-mediated activation of NF-κB[J]. Eur J Immunol, 2014, 44(2): 480-488. doi: 10.1002/eji.201343668
    [6]
    Murata M, Teshima T. Treatment of steroid-refractory acute graft-versus-host disease using commercial mesenchymal stem cell products[J]. Front Immunol, 2021, 12: 724380. doi: 10.3389/fimmu.2021.724380
    [7]
    Ling L, Feng XS, Wei TQ, et al. Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism[J]. Stem Cell Res Ther, 2019, 10(1): 46. doi: 10.1186/s13287-019-1136-x
    [8]
    Wang DD, Huang SS, Yuan XR, et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus[J]. Cell Mol Immunol, 2017, 14(5): 423-431. doi: 10.1038/cmi.2015.89
    [9]
    Wang DD, Li J, Zhang Y, et al. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study[J]. Arthritis Res Ther, 2014, 16(2): R79. doi: 10.1186/ar4520
    [10]
    Putra A, Alif I, Hamra N, et al. MSC-released TGF-β regulate α-SMA expression of myofibroblast during wound healing[J]. J Stem Cells Regen Med, 2020, 16(2): 73-79. doi: 10.46582/jsrm.1602011
    [11]
    Zong S, Liang CB. Evaluation of VEGF gene modified MSC in preventing intrauterine adhesion and promoting endometrial regeneration and repair[J]. Chin J Birth Health Hered (中国优生与遗传杂志), 2022, 30(1): 20-24.
    [12]
    Reagan MR, Seib FP, McMillin DW, et al. Stem cell implants for cancer therapy: trail-expressing mesenchymal stem cells target cancer cells in situ[J]. J Breast Cancer, 2012, 15(3): 273-282. doi: 10.4048/jbc.2012.15.3.273
    [13]
    Lou X, Gong EN, Shang FY, et al. Exploratory research for hepatocyte growth factor gene-modified mesenchymal stem cells on femoral head osteonecrosis[J]. J Tissue Eng Reconstr Surg (组织工程与重建外科杂志), 2009, 5(2): 83-85,107.
    [14]
    Baloh RH, Johnson JP, Avalos P, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial[J]. Nat Med, 2022, 28(9): 1813-1822. doi: 10.1038/s41591-022-01956-3
    [15]
    Ma YC, Wang T, Liao JX, et al. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study[J]. Stem Cell Res Ther, 2014, 5(5): 115. doi: 10.1186/scrt505
    [16]
    Hauzeur JP, De Maertelaer V, Baudoux E, et al. Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial[J]. Int Orthop, 2018, 42(7): 1429-1435. doi: 10.1007/s00264-017-3650-8
    [17]
    Houdek MT, Wyles CC, Collins MS, et al. Stem cells combined with platelet-rich plasma effectively treat corticosteroid-induced osteonecrosis of the hip: a prospective study[J]. Clin Orthop Relat Res, 2018, 476(2): 388-397. doi: 10.1007/s11999.0000000000000033
    [18]
    Nakao M, Inanaga D, Nagase K, et al. Characteristic differences of cell sheets composed of mesenchymal stem cells with different tissue origins[J]. Regen Ther, 2019, 11: 34-40. doi: 10.1016/j.reth.2019.01.002
    [19]
    Turinetto V, Vitale E, Giachino C. Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy[J]. Int J Mol Sci, 2016, 17(7): 1164. doi: 10.3390/ijms17071164
    [20]
    Wu TY, Xing ZG, Xie HX, et al. Difference in immune regulation ability of p5 human umbilical cord mesenchymal stem cells from different donor sources[J]. Chin J Exp Surg (中华实验外科杂志), 2022, 39(4): 3.
    [21]
    Zhou SH, Greenberger JS, Epperly MW, et al. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts[J]. Aging Cell, 2008, 7(3): 335-343. doi: 10.1111/j.1474-9726.2008.00377.x
    [22]
    Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood[J]. Br J Haematol, 2000, 109(1): 235-242. doi: 10.1046/j.1365-2141.2000.01986.x
    [23]
    Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord[J]. Stem Cells, 2003, 21(1): 105-110. doi: 10.1634/stemcells.21-1-105
    [24]
    Salehinejad P, Alitheen NB, Ali AM, et al. Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton’s jelly[J]. In Vitro Cell Dev Biol Anim, 2012, 48(2): 75-83. doi: 10.1007/s11626-011-9480-x
    [25]
    Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy, 2006, 8(4): 315-317. doi: 10.1080/14653240600855905
    [26]
    Krampera M, Galipeau J, Shi YF, et al. Immunological characterization of multipotent mesenchymal stromal cells: the International Society for Cellular Therapy (ISCT) working proposal[J]. Cytotherapy, 2013, 15(9): 1054-1061. doi: 10.1016/j.jcyt.2013.02.010
    [27]
    Liu HX, Yang Q, Xie H, et al. EP 9.2 2.6. 27. Microbiological examination of cell-based preparations[J]. Drug Stand China (中国药品标准), 2019, 20(2): 115-118.
    [28]
    CP “9406 Guiding Principles for Microbial Examination of Cellular Products”, Chinese Pharmacopoeia, 2020.
    [29]
    Zhao X, Feng JP, Meng SF. Considerations on mycoplasma detection by nucleic acid detection method and the methodological validation[J]. Chin Pharm Aff (中国药事), 2018, 32(8): 1020-1027.
    [30]
    WHO. World Health Organization Technical Report Series No. 987 Annex 3. 2013. In: Recommendations for the evaluation of animal cell cultures as substrates for the manufacture of biological medicinal products and for the characterization of cell bank.
    [31]
    Lee AS, Tang C, Rao MS, et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies[J]. Nat Med, 2013, 19(8): 998-1004. doi: 10.1038/nm.3267
    [32]
    Klopp AH, Gupta A, Spaeth E, et al. Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?[J]. Stem Cells, 2011, 29(1): 11-19. doi: 10.1002/stem.559
    [33]
    Lu JQ, Wei W, Liu BN, et al. Research progress, chemistry, manufacturing and controls considerations of mesenchymal stem cell products[J]. Acta Pharm Sin (药学学报), 2019, 54(7): 1317-1324.
    [34]
    Yamanaka S. Pluripotent stem cell-based cell therapy-promise and challenges[J]. Cell Stem Cell, 2020, 27(4): 523-531. doi: 10.1016/j.stem.2020.09.014
    [35]
    Han L, He H, Yang YH, et al. Distinctive clinical and pathologic features of immature teratomas arising from induced pluripotent stem cell-derived beta cell injection in a diabetes patient[J]. Stem Cells Dev, 2022, 31(5/6): 97-101.
    [36]
    Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration[J]. N Engl J Med, 2017, 376(11): 1038-1046. doi: 10.1056/NEJMoa1608368
    [37]
    Hayashi R, Ishikawa Y, Katayama T, et al. CD200 facilitates the isolation of corneal epithelial cells derived from human pluripotent stem cells[J]. Sci Rep, 2018, 8(1): 16550. doi: 10.1038/s41598-018-34845-2
    [38]
    Tsujisaka Y, Hatani T, Okubo C, et al. Purification of human iPSC-derived cells at large scale using microRNA switch and magnetic-activated cell sorting[J]. Stem Cell Reports, 2022, 17(7): 1772-1785. doi: 10.1016/j.stemcr.2022.05.003
    [39]
    Jeong HC, Cho SJ, Lee MO, et al. Technical approaches to induce selective cell death of pluripotent stem cells[J]. Cell Mol Life Sci, 2017, 74(14): 2601-2611. doi: 10.1007/s00018-017-2486-0
    [40]
    Kuroda T, Yasuda S, Sato Y. Tumorigenicity studies for human pluripotent stem cell-derived products[J]. Biol Pharm Bull, 2013, 36(2): 189-192. doi: 10.1248/bpb.b12-00970
    [41]
    Shi H, Feng TJ, Wang R, et al. Universal markers for hiPSCs residue detection[J]. Front Biosci (Landmark Ed), 2022, 27(8): 239. doi: 10.31083/j.fbl2708239
    [42]
    Merkle FT, Ghosh S, Kamitaki N, et al. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations[J]. Nature, 2017, 545(7653): 229-233. doi: 10.1038/nature22312
    [43]
    Avior Y, Lezmi E, Eggan K, et al. Cancer-related mutations identified in primed human pluripotent stem cells[J]. Cell Stem Cell, 2021, 28(1): 10-11. doi: 10.1016/j.stem.2020.11.013
    [44]
    Guo G, von Meyenn F, Austin S. Epigenetic resetting of human pluripotency[J]. Development, 2017, 144(15): 2748-2763. doi: 10.1016/j.biologicals.2014.11.007
    [45]
    Qu Z, Lin Z, Huo GT, et al. Risk assessment of tumorigenicity and oncogenicity of cell therapy products[J]. Chin J New Drugs (中国新药杂志), 2021, 30(19): 1819-1824.
    [46]
    Stirparo GG, Smith A, Guo G. Cancer-related mutations are not enriched in naive human pluripotent stem cells[J]. Cell Stem Cell, 2021, 28(1): 164-169. e2.
    [47]
    Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease[J]. Gastroenterology, 2018, 154(5): 1334-1342. e4.
    [48]
    Riordan NH, Morales I, Fernández G, et al. Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis[J]. J Transl Med, 2018, 16(1): 57. doi: 10.1186/s12967-018-1433-7
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