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https://doi.org/10.18502/wkmj.v65i4.14684
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-
Halimeh Mobarak
Halimeh Mobarak
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
-
Reza Rahbarghazi
Reza Rahbarghazi
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
-
Mahdi Mahdipour
Mahdi Mahdipour
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Published Date
- Dec 21, 2023
Stem Cell- and Stem Cell-Free-Based Therapies: Pros and Cons
Abstract
The efficiency of stem cell (SC)-based therapies has been proven in numerous animal and human studies. Along with the differentiation into several lineages, it is quite evident that SCs convey significant therapeutic effects in a paracrine manner via releasing various nano-sized extracellular vesicles (EVs) containing cytokines and bioactive factors. Notably, recent trials have stated the lack of stability and durability of the transplanted SCs at the site of injury for long periods, leading to the restrictions of SC in regenerative outcomes. Thus, EVs especially exosomes (Exos) gained much attention for therapeutic purposes and delivery purposes to the injury site. In contrast to whole-SC-based therapies, Exos can be used with fewer side effects. However, it should not be forgotten that both whole-SC- and cell-free-based options possess inherent pros and cons that necessitate being carefully evaluated before application in the clinical setting. Here, the effectiveness and limitations associated with whole-SCand SC-free-based therapies in the clinical setting are briefly discussed.
Keywords:
stem cell transplantation, cell-free system, exosomes, regenerative medicine, immune evasion
References
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[25] Mobarak H, Heidarpour M, Rahbarghazi R, Nouri M, Mahdipour M. Amniotic fluidderived exosomes improved spermatogenesis in a rat model of azoospermia. Life Sci. 2021;274:119336.
[26] Yamchi NN, Ahmadian S, Mobarak H, Amjadi F, Beheshti R, Tamadon A, et al. Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway. J Ovarian Res. 2023;16(1):118.
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[28] Li J, Li J, Peng Y, Du Y, Yang Z, Qi X. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J Control Release. 2023;353:423-433.
[29] Pachler K, Lener T, Streif D, Dunai ZA, Desgeorges A, Feichtner M, et al. A good manufacturing practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017;19(4):458-72.
[30] Krueger TEG, Thorek DLJ, Denmeade SR, Isaacs JT, Brennen WN. Concise review: mesenchymal stem cell-based drug delivery: The good, the bad, the ugly, and the promise. Stem Cells Transl Med. 2018;7(9):651-663.
[31] Walker S, Busatto S, Pham A, Tian M, Suh A, Carson K, et al. Extracellular vesiclebased drug delivery systems for cancer treatment. Theranostics. 2019;9(26):8001- 8017.
[32] Lener T, Gimona M, Aigner L, Borger V, Buzas E, Camussi G, et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles. 2015;4(1):30087.
[2] Csöbönyeiová M, Beerová N, Klein M, Debreová-Čeháková M, Danišovič Ľ. Cell- Based and Selected Cell-Free Therapies for Myocardial Infarction: How Do They Compare to the Current Treatment Options? Int J Mol Sci. 2022;23(18):10314.
[3] Malik S, Malik T. Mesenchymal Stem Cells Lysate as a Cell-Free Therapy: A Review. Curr Biotechnol. 2021;10(2):78-87.
[4] Zhao X, Wang W, Nie S, Geng L, Song K, Zhang X, et al. Dynamic comparison of early immune reactions and immune cell reconstitution after umbilical cord blood transplantation and peripheral blood stem cell transplantation. Front Immunol. 2023;14:1084901.
[5] Yamchi NN, Rahbarghazi R, Bedate AM, Mahdipour M, Nouri M, Khanbabaee R. Menstrual blood CD146(+) mesenchymal stem cells reduced fibrosis rate in the rat model of premature ovarian failure. Cell Biochem Funct. 2021;39(8):998-1008.
[6] Sheshpari S, Shahnazi M, Ahmadian S, Nouri M, Mesgari Abbasi M, Beheshti R, et al. Intra-ovarian injection of bone marrow-derived c-Kit(+) cells for ovarian rejuvenation in menopausal rats. Bioimpacts. 2022;12(4):325-35.
[7] Matsushita Y, Liu J, Chu AKY, Tsutsumi-Arai C, Nagata M, Arai Y, et al. Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis. Nat Commun. 2023;14(1):2383.
[8] Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019;10(1):68.
[9] Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noel D. Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications. Stem Cell Res Ther. 2010;1(1):2.
[10] Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood. 2005;106(13):4057-65.
[11] Chan TS, Khong PL, Kwong YL. Pembrolizumab for relapsed anaplastic large cell lymphoma after allogeneic haematopoietic stem cell transplantation: efficacy and safety. Ann Hematol. 2016;95(11):1913-5.
[12] Serakinci N, Tulay P, Kalkan R. Role of Mesenchymal Stem Cells in Cancer Development and Their Use in Cancer Therapy. Adv Exp Med Biol. 2018;1083:45-62.
[13] Mathew E, Brannon AL, Del Vecchio A, Garcia PE, Penny MK, Kane KT, et al. Mesenchymal stem cells promote pancreatic tumor growth by inducing alternative polarization of macrophages. Neoplasia. 2016;18(3):142-151.
[14] Parfejevs V, Sagini K, Buss A, Sobolevska K, Llorente A, Riekstina U, et al. Adult Stem Cell-Derived Extracellular Vesicles in Cancer Treatment: Opportunities and Challenges. Cells. 2020;9(5):1171.
[15] Gao S, Zhang Y, Liang K, Bi R, Du Y. Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes. Stem Cells Int. 2022;2022:8637493.
[16] Holloway MR, Fountaine T, Henrichs K, Feeney T, Andolina J, O’Dwyer K, et al. Association of crystalloid fluid infusion with intravascular hemolysis and organ dysfunction in hematopoietic stem cell transplant patients. Transfus Apher Sci. 2023;62(3):103641.
[17] Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, et al. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38(7):961- 967.
[18] Foo JB, Looi QH, Chong PP, Hassan NH, Yeo GEC, Ng CY, et al. Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine. Stem Cells Int. 2021;2021:2616807.
[19] Maron-Gutierrez T, Rocco PRM. Cell-free therapies: Novel approaches for COVID-19. Front Immunol. 2020;11:583017.
[20] Sadeghi S, Tehrani FR, Tahmasebi S, Shafiee A, Hashemi SM. Exosome engineering in cell therapy and drug delivery. Inflammopharmacology. 2023;31(1):145-169.
[21] Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP. Isolation of extracellular vesicles: General methodologies and latest trends. Biomed Res Int. 2018;2018:8545347.
[22] Masoumipour M, Abbaspanah B, Mousavi SH. Extracellular vesicles: Regenerative medicine prospect in hematological malignancies. Cell Biol Int. 2021;45(10):2031- 2044.
[23] Lu Y, Mai Z, Cui L, Zhao X. Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration. Stem Cell Res Ther. 2023;14(1):55.
[24] Tracy EP, Stielberg V, Rowe G, Benson D, Nunes SS, Hoying JB, et al. State of the field: cellular and exosomal therapeutic approaches in vascular regeneration. Am J Physiol Heart Circ Physiol. 2022;322(4):H647-H80.
[25] Mobarak H, Heidarpour M, Rahbarghazi R, Nouri M, Mahdipour M. Amniotic fluidderived exosomes improved spermatogenesis in a rat model of azoospermia. Life Sci. 2021;274:119336.
[26] Yamchi NN, Ahmadian S, Mobarak H, Amjadi F, Beheshti R, Tamadon A, et al. Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway. J Ovarian Res. 2023;16(1):118.
[27] Wang TQ, Fu YA, Sun SJ, Huang CY, Yi YF, Wang JQ, et al. Exosome-based drug delivery systems in cancer therapy. Chin Chem Lett. 2023;34(2):107508.
[28] Li J, Li J, Peng Y, Du Y, Yang Z, Qi X. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J Control Release. 2023;353:423-433.
[29] Pachler K, Lener T, Streif D, Dunai ZA, Desgeorges A, Feichtner M, et al. A good manufacturing practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017;19(4):458-72.
[30] Krueger TEG, Thorek DLJ, Denmeade SR, Isaacs JT, Brennen WN. Concise review: mesenchymal stem cell-based drug delivery: The good, the bad, the ugly, and the promise. Stem Cells Transl Med. 2018;7(9):651-663.
[31] Walker S, Busatto S, Pham A, Tian M, Suh A, Carson K, et al. Extracellular vesiclebased drug delivery systems for cancer treatment. Theranostics. 2019;9(26):8001- 8017.
[32] Lener T, Gimona M, Aigner L, Borger V, Buzas E, Camussi G, et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles. 2015;4(1):30087.