Abstract
According to the World Health Organization (WHO), about 3.9 million people die annually of ischemic heart disease (IHD). Several clinical trials have shown that stem cell therapy is a promising therapeutic approach to IHD. Human amniotic membrane mesenchymal stem cells (hAMSCs) positively affect the repair of myocardial ischemia–reperfusion (MI/R) injury by stimulating endogenous repair mechanisms. The differentiated hAMSCs with and without modified PGS-co-PCL film were applied in the myocardium. MI/R injury was induced by ligating the left anterior descending artery in 48 male Wistar rats. The rats were divided into four groups, (n = 12) animals: heart failure (HF) as the control group, HF + MSCs, HF + MSCs + film, and HF + film. Echocardiography was performed 2 and 4 weeks after MI/R injury moreover the expression of the VEGF protein was assessed in the rat heart tissue via immunohistochemistry. In vitro, our result shows fantastic cell survival when seeded on film. In vivo, the left ventricle ejection fraction (LEVD), fractional shortening (FS), end-diastolic (EDV), and stroke volume (SV) have been increased and systolic volumes decreased in all treatment groups in comparison with control. Although combination therapy has a more positive effect on hemodynamic parameters, there is no significant difference between HF + MSCs + film with other treatment groups. Also, In the IHC assay, expression of the VEGF protein significantly increased in all intervention groups. The implantation of MSCs and the modified film significantly enhanced the cardiac functional outcome; in this regard, enhancement in cell survival and VEGF expression are involved as underlying mechanisms in which cardiac film and MSCs exert a beneficial effect.
Similar content being viewed by others
Data Availability
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
References
Ramesh, S., Govarthanan, K., Ostrovidov, S., Zhang, H., Hu, Q., Camci-Unal, G., Ramalingam, M. (2021). Cardiac differentiation of mesenchymal stem cells: impact of biological and chemical inducers. Stem Cell Reviews and Reports, 17(4), 1343–1361. https://doi.org/10.1007/s12015-021-10165-3
Zanjanizadeh Ezazi, N., Ajdary, R., Correia, A., Makila, E., Salonen, J., Kemell, M., Santos, H. A. (2020). Fabrication and characterization of drug-loaded conductive poly(glycerol sebacate)/nanoparticle-based composite patch for myocardial infarction applications. ACS Applied Material and Interfaces, 12(6), 6899–6909. https://doi.org/10.1021/acsami.9b21066
Jennings, D. L., Lange, N., Shullo, M., Latif, F., Restaino, S., Topkara, V. K., Takeda, K., Takayama, H., Naka, Y., Farr, M., Colombo, P., & Baker, W. L. (2018). Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis. International Journal of Cardiology, 265, 71–76. https://doi.org/10.1016/j.ijcard.2018.03.111
Hao, M., Wang, R., & Wang, W. (2017). Cell therapies in cardiomyopathy: Current status of clinical trials. Analytical Cellular Pathology (Amsterdam), 2017, 9404057. https://doi.org/10.1155/2017/9404057.
White, S. J., & Chong, J. J. H. (2020). Mesenchymal stem cells in cardiac repair: Effects on myocytes, vasculature, and fibroblasts. Clinical Therapeutics, 42(10), 1880–1891. https://doi.org/10.1016/j.clinthera.2020.08.010.
Maheshwer, B., Polce, E. M., Paul, K., Williams, B. T., Wolfson, T. S., Yanke, A., Chahla, J. (2021). Regenerative potential of mesenchymal stem cells for the treatment of knee osteoarthritis and chondral defects: A systematic review and meta-analysis. Arthroscopy, 37(1), 362–378. https://doi.org/10.1016/j.arthro.2020.05.037
Zhang, J., Liang, R., Wang, K., Zhang, W., Zhang, M., Jin, L., Zhang, Y. (2022). Novel CaMKII-delta inhibitor hesperadin exerts dual functions to ameliorate cardiac ischemia/reperfusion injury and inhibit tumor growth. Circulation, 145(15), 1154–1168. https://doi.org/10.1161/CIRCULATIONAHA.121.055920
Ronaldson-Bouchard, K., Ma, S. P., Yeager, K., Chen, T., Song, L., Sirabella, D., Vunjak-Novakovic, G. (2018). Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature, 556(7700), 239–243. https://doi.org/10.1038/s41586-018-0016-3
Shen, Z., Guo, Z., Tan, T., Hu, J., & Zhang, Y. (2020). Reactive oxygen species scavenging and biodegradable peptide hydrogel as 3D culture scaffold for cardiomyocytes. ACS Biomaterials Science & Engineering, 6(7), 3957–3966. https://doi.org/10.1021/acsbiomaterials.0c00340.
Gao, L., Yi, M., Xing, M., Li, H., Zhou, Y., Xu, Q., Chang, J. (2020). In situ activated mesenchymal stem cells (MSCs) by bioactive hydrogels for myocardial infarction treatment. Journal of Materials Chemistry B. https://doi.org/10.1039/d0tb01320j
Rashedi, I., Talele, N., Wang, X. H., Hinz, B., Radisic, M., & Keating, A. (2017). Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells. PLoS One, 12(10), e0187348. https://doi.org/10.1371/journal.pone.0187348
Li, X., Ma, T., Sun, J., Shen, M., Xue, X., Chen, Y., & Zhang, Z. (2019). Harnessing the secretome of adipose-derived stem cells in the treatment of ischemic heart diseases. Stem Cell Research and Therapy, 10(1), 196. https://doi.org/10.1186/s13287-019-1289-7.
Shafei AE, Ali MA, Ghanem HG, Shehata AI, Abdelgawad AA, Handal HR, Talaat KA, Ashaal AE, El-Shal AS.(2017). Mesenchymal stem cell therapy: A promising cell-based therapy for treatment of myocardial infarction. The Journal of Gene Medicine, 19(12). https://doi.org/10.1002/jgm.2995.2017
Wang, W., Tayier, B., Guan, L., Yan, F., & Mu, Y. (2022). Pre-transplantation of bone marrow mesenchymal stem cells amplifies the therapeutic effect of ultrasound-targeted microbubble destruction-mediated localized combined gene therapy in post-myocardial infarction heart failure rats. Ultrasound in Medicine and Biology, 48(5), 830–845. https://doi.org/10.1016/j.ultrasmedbio.2022.01.004.
Cristallini, C., Vaccari, G., Barbani, N., Cibrario Rocchietti, E., Barberis, R., Falzone, M., Giachino, C. (2019). Cardioprotection of PLGA/gelatine cardiac patches functionalised with adenosine in a large animal model of ischaemia and reperfusion injury: A feasibility study. Journal of Tissue Engineering and Regenerative Medicine, 13(7), 1253–1264. https://doi.org/10.1002/term.2875
Lee, J. R., Park, B. W., Kim, J., Choo, Y. W., Kim, H. Y., Yoon, J. K., Kim, B. S. (2020). Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair. Science Advance, 6(18), eaaz0952. https://doi.org/10.1126/sciadv.aaz0952
Khan, K., Makhoul, G., Yu, B., Jalani, G., Derish, I., Rutman, A. K., Cecere, R. (2022). Amniotic stromal stem cell-loaded hydrogel repairs cardiac tissue in infarcted rat hearts via paracrine mediators. Journal of Tissue Engineering and Regenerative Medicine, 16(2), 110–127. https://doi.org/10.1002/term.3262
Liu, J., Zhou, X., Meng, Q., Huang, K. W., Liu, J., Tie, J., Liu, Z. (2019). AFC1 Compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway. Frontier in Pharmacology, 10, 1142. https://doi.org/10.3389/fphar.2019.01142
Zhou, Z., Zhang, S., Ding, S., Abudupataer, M., Zhang, Z., Zhu, X., Hong, T. (2019). Excessive neutrophil extracellular trap formation aggravates acute myocardial infarction injury in apolipoprotein E deficiency mice via the ROS-dependent pathway. Oxidative Medicine and Cellular Longevity, 2019, 1209307. https://doi.org/10.1155/2019/1209307
HoomanGolbaten, MofradaAlirezaSeyfi, SahzabibSabaSeyfikar, HadiSalehi, M., VahabodinGoodarzi, R.Wurm, F., & HassanJafari, S. (2021). Facile template preparation of novel electroactive scaffold composed of polypyrrole-coated poly(glycerol-sebacate-urethane) for tissue engineering applications.
Azizipour, E., Aghamollaei, H., Halabian, R., Poormoghadam, D., Saffari, M., Entezari, M., & Salimi, A. (2021). A novel hydrogel scaffold contained bioactive glass nanowhisker (BGnW) for osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro. International Journal of Biological Macromolecules, 174, 562–572. https://doi.org/10.1016/j.ijbiomac.2021.01.002.
Naeemi, S., Eidi, A., Khanbabaee, R., Sadri-Ardekani, H., & Kajbafzadeh, A. M. (2021). Differentiation and proliferation of spermatogonial stem cells using a three-dimensional decellularized testicular scaffold: A new method to study the testicular microenvironment in vitro. International Urology and Nephrology, 53(8), 1543–1550. https://doi.org/10.1007/s11255-021-02877-9.
Nagaya, N., Fujii, T., Iwase, T., Ohgushi, H., Itoh, T., Uematsu, M., Kitamura, S. (2004). Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. American Journal of Physiology-Heart and Circulatory, 287(6), H2670–2676. https://doi.org/10.1152/ajpheart.01071.2003
Chen, M., Chen, J., Huang, W., Li, C., Luo, H., Xue, Z., Chen, C. (2022). Exosomes from human induced pluripotent stem cells derived mesenchymal stem cells improved myocardial injury caused by severe acute pancreatitis through activating Akt/Nrf2/HO-1 axis. Cell Cycle, 1–12. https://doi.org/10.1080/15384101.2022.2057762
Hu, J., Chen, X., Li, P., Lu, X., Yan, J., Tan, H., & Zhang, C. (2021). Exosomes derived from human amniotic fluid mesenchymal stem cells alleviate cardiac fibrosis via enhancing angiogenesis in vivo and in vitro. Cardiovascular Diagnosis and Therapy, 11(2), 348–361. https://doi.org/10.21037/cdt-20-1032
Orticelli, V., Papait, A., Vertua, E., Bonassi Signoroni, P., Romele, P., Di Pietro, L., Parolini, O. (2021). Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells. Stem Cells Translational Medicine, 10(11), 1516–1529. https://doi.org/10.1002/sctm.21-0130
Prieto, P., Fernandez-Velasco, M., Fernandez-Santos, M. E., Sanchez, P. L., Terron, V., Martin-Sanz, P., Bosca, L. (2016). Cell expansion-dependent inflammatory and metabolic profile of human bone marrow mesenchymal stem cells. Frontier in Physiology, 7, 548. https://doi.org/10.3389/fphys.2016.00548
Yusoff, N. H., Alshehadat, S. A., Azlina, A., Kannan, T. P., & Hamid, S. S. (2015). A Comparison of culture characteristics between human amniotic mesenchymal stem cells and dental stem cells. Tropical Life Science Research, 26(1), 21–29.
Shi, S., Wu, X., Wang, X., Hao, W., Miao, H., Zhen, L., & Nie, S. (2016). Differentiation of bone marrow mesenchymal stem cells to cardiomyocyte-like cells is regulated by the combined low dose treatment of transforming growth factor-β1 and 5-azacytidine. Stem Cells International, 2016, 3816256. https://doi.org/10.1155/2016/3816256
He, X., Wang, Q., Zhao, Y., Zhang, H., Wang, B., Pan, J., ... Wang, D. (2020). Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease: A randomized clinical trial. JAMA Network Open, 3(9), e2016236. https://doi.org/10.1001/jamanetworkopen.2020.16236
Hoveizi, E., & Tavakol, S. H. (2022). Differentiation of human Wharton’s jelly mesenchymal stem cells into SOX17 expressing cells using a Wnt/ss-catenin pathway agonist on polylactic acid/chitosan nanocomposite scaffold. Cell Journal, 24(2), 55–61. https://doi.org/10.22074/cellj.2022.7622
Alonzo, M., AnilKumar, S., Roman, B., Tasnim, N., & Joddar, B. (2019). 3D Bioprinting of cardiac tissue and cardiac stem cell therapy. Translational Research: The Journal of Laboratory and Clinical Medicine, 211, 64–83. https://doi.org/10.1016/j.trsl.2019.04.004
Kishta, M. S., Ahmed, H. H., Ali, M. A. M., Aglan, H. A., & Mohamed, M. R. (2021). Mesenchymal stem cells seeded onto nanofiber scaffold for myocardial regeneration. Biotechnology Histochemistry, 1–12. https://doi.org/10.1080/10520295.2021.1979251
Thavapalachandran, S., Le, T. Y. L., Romanazzo, S., Rashid, F. N., Ogawa, M., Kilian, K. A.,. Chong, J. J. H. (2021). Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction. Cytotherapy, 23(12), 1074–1084. https://doi.org/10.1016/j.jcyt.2021.07.016
Kobayashi, K., Ichihara, Y., Sato, N., Umeda, N., Fields, L., Fukumitsu, M., Suzuki, K. (2019). On-site fabrication of Bi-layered adhesive mesenchymal stromal cell-dressings for the treatment of heart failure. Biomaterials, 209, 41–53. https://doi.org/10.1016/j.biomaterials.2019.04.014
Lancaster, J. J., Sanchez, P., Repetti, G. G., Juneman, E., Pandey, A. C., Chinyere, I. R., Goldman, S. (2019). Human induced pluripotent stem cell-derived cardiomyocyte patch in rats with heart failure. The Annals of Thoracic Surgery, 108(4), 1169–1177. https://doi.org/10.1016/j.athoracsur.2019.03.099
Schmuck, E. G., Hacker, T. A., Schreier, D. A., Chesler, N. C., & Wang, Z. (2019). Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats. American Journal of Physiology. Heart and Circulatory Physiology, 316(5), H1005–H1013. https://doi.org/10.1152/ajpheart.00091.2018.
Abbasgholizadeh, R., Islas, J. F., Navran, S., Potaman, V. N., Schwartz, R. J., & Birla, R. K. (2020). A highly conductive 3D cardiac patch fabricated using cardiac myocytes reprogrammed from human adipogenic mesenchymal stem cells. Cardiovascular Engineering and Technology, 11(2), 205–218. https://doi.org/10.1007/s13239-019-00451-0.
Jackson, A. O., Rahman, G. A., Yin, K., & Long, S. (2021). Enhancing matured stem-cardiac cell generation and transplantation: A novel strategy for heart failure therapy. Journal of Cardiovascular Translational Research, 14(3), 556–572. https://doi.org/10.1007/s12265-020-10085-6.
Yeung, E., Fukunishi, T., Bai, Y., Bedja, D., Pitaktong, I., Mattson, G., Hibino, N. (2019). Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo. The Open Tissue Engineering and Regenerative Medicine Journal, 13(11), 2031–2039. https://doi.org/10.1002/term.2954
Shukla, A., Choudhury, S., Chaudhary, G., Singh, V., Prabhu, S. N., Pandey, S., & Garg, S. K. (2021). Chitosan and gelatin biopolymer supplemented with mesenchymal stem cells (Velgraft(R)) enhanced wound healing in goats (Capra hircus): Involvement of VEGF, TGF and CD31. Journal of Tissue Viability, 30(1), 59–66. https://doi.org/10.1016/j.jtv.2020.12.002.
Gorjipour, F., Hosseini-Gohari, L., Alizadeh Ghavidel, A., Hajimiresmaiel, S. J., Naderi, N., Darbandi Azar, A., & Pazoki-Toroudi, H. (2019). Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure. Journal of Cardiovascular and Thoracic Research, 11(1), 35–42. https://doi.org/10.15171/jcvtr.2019.06
Monguió-Tortajada, M., Prat-Vidal, C., Martínez-Falguera, D., Teis, A., Soler-Botija, C., Courageux, Y., & Gálvez-Montón, C. (2022). Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles limit ventricular remodelling and exert local and systemic immunomodulation in a myocardial infarction porcine model. Theranostics, 12(10), 4656–4670. https://doi.org/10.7150/thno.72289
Poomani, M. S., Mariappan, I., Perumal, R., Regurajan, R., Muthan, K., & Subramanian, V. (2022). Mesenchymal stem cell (MSCs) therapy for ischemic heart disease: A promising frontier. Global Heart, 17(1), 19. https://doi.org/10.5334/gh.1098
Acknowledgements
The authors would like to thank Dr. Gudarzi for the film design and construction.
Author information
Authors and Affiliations
Contributions
All the authors have collaborated and participated in writing all parts of the manuscript.
Corresponding author
Ethics declarations
Ethics Approval
All animal protocols complied with the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health and carried out under the supervision of the Animal Work Ethics Committee of Islamic Azad University of Medical Sciences (IR.IAU.PS.REC.1400.559).
Competing Interests
The authors declare no competing interests.
Consent for Publication
The authors have given consent for the publication of this manuscript.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Bahrami, N., Ale-Ebrahim, M., Asadi, Y. et al. Combined Application of Human Amniotic Membrane Mesenchymal Stem Cells and a Modified PGS-co-PCL Film in an Experimental Model of Myocardial Ischemia–Reperfusion Injury. Appl Biochem Biotechnol 195, 7502–7519 (2023). https://doi.org/10.1007/s12010-023-04446-5
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-023-04446-5