Progress in Application of Hydrogels and Mesenchymal Stem Cells in Tissue Engineering
Li Min1, Meng Xiangjing1#*, Zhang Xiangkui1, Liu Bo1, Duan Chonggang1, Zhang Lanying1, Zhang Daizhou1, Ling Peixue1, 2
1 Shandong Provincial Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China; 2 Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Freda Pharmaceutical Group Co., Ltd., Jinan 250101, China
Abstract：With the development of tissue engineering, there is an increasing focus on using hydrogel as scaffolds and 3D culture modes for tissue and organ regeneration. Hydrogel is formed by hydrophilic polymer, copolymer or a monomer macromolecule capable of forming a macromolecular chain, which can absorb a large amount of water and maintain a three-dimensional structure. Because of its good biocompatibility, entrapment of cells and bioactive molecules and effective delivery, they are widely used in drug delivery, tissue engineering and so on in the field of biomedicine. Mesenchymal stem cells can be obtained in bone marrow, fat, umbilical cord and other tissues with low immunogenicity and multidirectional differentiation potential, which are the preferred cells for 3D cultures and cell therapies. At present, the culture mode of mesenchymal stem cells is mainly 2D. The 2D culture mode of mesenchymal stem cells leads to low reproduction rate and cannot simulate the growth environment in vivo. Hydrogel materials as scaffolds of 3D culture have good compatibility, can simulate the growth environment in vivo, and have great potential in repairing damaged cartilage, such as bone, skin and heart tissues. In this review, we summarized the applications of hydrogels and mesenchymal stem cells in tissue engineering. We showed the development of hydrogel materials and 3D culture mode of mesenchymal stem cells in different tissues, showing that the 3D culture mode of hydrogel materials and mesenchymal stem cells makes it possible to regenerate and repair tissues and organs, and providing a reference for the further study of the application of hydrogel and stem cell.
[1] Kopecek J. Hydrogel biomaterials: a smart future? [J]. Biomaterials, 2007, 28(34):5185-5192. [2] Mohammed EEA, Beherei HH, El-Zawahry M, et al. Combination of human amniotic fluid derived-mesenchymal stem cells and nano-hydroxyapatite scaffold enhances bone regeneration [J]. Open Access Maced J Med Sci, 2019, 7(17):2739-2750. [3] Li Ling, He Zhiyao, Wei Xiawei, et al. Recent advances of biomaterials in biotherapy [J]. Regen Biomater, 2016, 3(2): 99-105. [4] Arakawa C, Ng R, Tan S, et al. Photopolymerizable chitosan-collagen hydrogels for bone tissue engineering [J]. J Tissue Eng Regen Med, 2017, 11(1):164-174. [5] Murphy KC, Whitehead J, Zhou D, et al. Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids [J]. Acta Biomater, 2017, 64:176-186. [6] Zaviskova K, Tukmachev D, Dubisova J, et al. Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair[J]. J Biomed Mater Res A, 2018, 106(4):1129-1140. [7] Kim KD, Wright NM. Polyethylene glycol hydrogel spinal sealant (DuraSeal Spinal Sealant) as an adjunct to sutured dural repair in the spine: Results of a prospective, multicenter, randomized controlled study [J]. Spine (Phila Pa 1976), 2011, 36(23):1906-1912. [8] Aijaz A, Teryek M, Goedken M, et al. Coencapsulation of ISCs and MSCs enhances viability and function of both cell types for improved wound healing [J]. Cell Mol Bioeng, 2019, 12(5):481-493. [9] Oh JK. Engineering of nanometer-sized cross-linked hydrogels for biomedical applications [J]. Can J Chem, 2010, 88(3):173-184. [10] Kim H, Bae C, Kook YM, et al. Mesenchymal stem cell 3D encapsulation technologies for biomimetic microenvironment in tissue regeneration [J]. Stem Cell Res Ther, 2019, 10(1):51-64. [11] Seo KD, Choi A, Doh J, et al. Synthesis of poly(N-isopropylacrylamide) janus microhydrogels for anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability [J]. J Vis Exp, 2016, 27(108):52813-52823. [12] Qayyum AS, Jain E, Kolar G, et al. Design of electrohydrodynamic sprayed polyethylene glycol hydrogel microspheres for cell encapsulation [J]. Biofabrication, 2017, 9(2):025019. [13] Zhu Junmin, Marchant RE. Design properties of hydrogel tissue-engineering scaffolds [J]. Expert Rev Med Devices, 2011, 8(5):607-626. [14] Brandl F, Sommer F, Goepferich A. Rational design of hydrogels for tissue engineering: Impact of physical factors on cell behavior [J]. Biomaterials, 2007, 28(2):134-146. [15] Hunt NC, Grover LM. Cell encapsulation using biopolymer gels for regenerative medicine [J]. Biotechnol Lett, 2010, 32(6):733-742. [16] Dias AD, Elicson JM, Murphy WL. Microcarriers with synthetic hydrogel surfaces for stem cell expansion [J]. Adv Healthc Mater, 2017, 6(16):1-20. [17] Takezawa T, Mori Y, Yoshizato K. Cell culture on a thermo-responsive polymer surface [J]. Nat Biotechnol, 1990, 8(9):854-856. [18] Vihola H, Laukkanen A, Valtola L, et al. Cytotoxicity of thermosensitive polymers poly(N-isopropylacrylamide), poly(N-vinylcaprolactam) and amphiphilically modified poly(N-vinylcaprolactam) [J]. Biomaterials, 2005, 26(16):3055-3064. [19] Buxton AN, Zhu Junmin, Marchant RE, et al. Design and characterization of poly (ethylene glycol) photopolymerizable semi-interpenetrating networks for chondrogenesis of human mesenchymal stem cells [J]. Tissue Eng, 2007, 13(10):2549-2560. [20] Higuchi A, Aoki N, Yamamoto T, et al. Temperature-induced cell deattachment on immobilized pluronic surface [J]. J Biomed Mater Res A, 2006, 79(2):380-392. [21] Whiteside TL. Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment [J]. Semin Immunol, 2018, 35:69-79. [22] Wang Yongzhong, Kim HJ, Vunjak-Novakovic G, et al. Stem cell-based tissue engineering with silk biomaterials [J]. Biomaterials, 2006, 27(36):6064-6082. [23] 李乔乔, 吴振强, 张丽君. 骨髓间充质干细胞的定向分化潜能 [J].中国组织工程研究, 2017, 21(25):4082-4087. [24] Amati E, Perbellini O, Rotta G, et al. High-throughput immunophenotypic characterization of bone marrow- and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers: Identification of angiotensin-converting enzyme (CD143) as a marker differentially expressed between adult and perinatal tissue sources [J]. Stem Cell Res Ther, 2018, 9(1):10. [25] 赵娜. 脂肪干细胞诱导分化的现状及前景 [J].中国组织工程研究, 2015, 19(6):969-974. [26] 刘岱, 赵玉明, 晏晓青, 等. 人脐带血间充质干细胞分离培养体系的优化筛选 [J].中国组织工程研究与临床康复, 2009, 13(10):1839-1843. [27] Goodwin HS, Bicknese AR, Chien SN, et al. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers [J]. Biol Blood Marrow Transplant, 2001, 7(11):581-588. [28] 王菲, 周洪, 郭昱成, 等. 原代人脐带间充质干细胞培养方法的研究 [J]. 中国组织工程研究, 2014, 18(19):3042-3047. [29] Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue [J]. Stem Cells, 2006, 24(5):1294-1301. [30] Secunda R, Vennila R, Mohanashankar AM, et al. Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study [J]. Cytotechnology, 2015, 67(5):793-807. [31] Gomzikova MO, James V, Rizvanov AA, et al. Therapeutic application of mesenchymal stem cells derived extracellular vesicles for immunomodulation [J]. Front Immunol, 2019, 10:2663. [32] Dabrowski FA, Burdzinska A, Kulesza A, et al. Comparison of the paracrine activity of mesenchymal stem cells derived from human umbilical cord, amniotic membrane and adipose tissue [J]. J Obstet Gynaecol Res, 2017, 43(11):1758-1768. [33] Du Wenjing, Chi Ying, Yang Zhouxin, et al. Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta [J]. Stem Cell Res Ther, 2016, 7(1):163. [34] Arévalo-Turrubiarte M, Olmeo C, Accornero P, et al. Analysis of mesenchymal cells (MSCs) from bone marrow, synovial fluid and mesenteric, neck and tail adipose tissue sources from equines [J]. Stem Cell Res, 2019, 37:101442. [35] Mahmoudian-Sani MR, Mehri-Ghahfarrokhi A, Hashemzadeh-Chaleshtori M, et al. Comparison of Three types of mesenchymal stem cells (bone marrow, adipose tissue, and umbilical cord-derived) as potential sources for inner ear regeneration [J]. Int Tinnitus J, 2017, 21(2):122-127. [36] Parmar PA, Skaalure SC, Chow LW, et al. Temporally degradable collagen-mimetic hydrogels tuned to chondrogenesis of human mesenchymal stem cells [J]. Biomaterials, 2016, 99:56-71. [37] Brunelle AR, Horner CB, Low K, et al. Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells [J]. Acta Biomater, 2018, 15(66):166-176. [38] Yuan Xiaoning, Wei Yiyong, Villasante A, et al. Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model [J]. Biomaterials, 2017, 132:59-71. [39] Amann E, Wolff P, Breel E, et al. Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures [J]. Acta Biomater, 2017, 52:130-144. [40] Zhao Chen, Zeng Zongyue, Qazvini NT, et al. Thermoresponsive citrate-based graphene oxide scaffold enhances bone regeneration from BMP9-stimulated adipose-derived mesenchymal stem cells [J]. ACS Biomater Sci Eng, 2018, 4(8):2943-2955. [41] Chen Xuebin, Zhang Fang, He Xinhong, et al. Chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells in type I collagen-hydrogel for cartilage engineering [J]. Injury, 2013, 44(4):540-549. [42] Park YB, Ha CW, Lee CH, et al. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up [J]. Stem Cells Transl Med, 2017, 6(2):613-621. [43] Park YB, Ha CW, Lee CH, et al. Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: A case report with a 5-year follow-up [J]. BMC Musculoskelet Disord, 2017, 18(1):59-67. [44] Zhang Lei, Gurankit Singh, Zhang Min, et al. Bone marrow-derived mesenchymal stem cells laden novel thermo-sensitive hydrogel for the management of severe skin wound healing [J]. Mater Sci Eng C Mater Biol Appl, 2018, 90:159-167. [45] Kim YH, Tabata Y. Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure [J]. J Biomed Mater Res A, 2016, 104(4):942-956. [46] Chen Shixuan, Shi Junbin, Zhang Min, et al. Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing [J]. Sci Rep, 2015, 5:18104-18116. [47] Alapure BV, Lu Yan, He Mingyu, et al. Accelerate healing of severe burn wounds by mouse bone marrow mesenchymal stem cell-seeded biodegradable hydrogel scaffold synthesized from arginine-based poly (ester amide) and chitosan [J]. Stem Cells Dev, 2018, 27(23):1605-1620. [48] Kosaraju R, Rennert RC, Maan ZN, et al. Adipose-derived stem cell-seeded hydrogels increase endogenous progenitor cell recruitment and neovascularization in wounds [J]. Tissue Eng Part A, 2016, 22(3-4):295-305. [49] Zhang Xiaofei, Li Jun, Ye Pengxiang, et al. Coculture of mesenchymal stem cells and endothelial cells enhances host tissue integration and epidermis maturation through AKT activation in gelatin methacryloyl hydrogel-based skin model [J]. Acta Biomater, 2017, 59:317-326. [50] Lee C, Shim S, Jang H, et al. Human umbilical cord blood-derived mesenchymal stromal cells and small intestinal submucosa hydrogel composite promotes combined radiation-wound healing of mice [J]. Cytotherapy, 2017, 19(9):1048-1059. [51] Xu Bin, Li Yang, Deng Bo, et al. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats [J]. Exp Ther Med, 2017, 13(2):588-594. [52] Mathieu E, Lamirault G, Toquet C, et al. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction [J]. PLoS ONE, 2012, 7(12):e51991. [53] Ichihara Y, Kaneko M, Yamahara K, et al. Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure [J]. Biomaterials, 2018, 154:12-23. [54] Li Zhenqing, Guo Xiaolei, Guan Jianjun. A thermosensitive hydrogel capable of releasing bFGF for enhanced differentiation of mesenchymal stem cell into cardiomyocyte-like cells under ischemic conditions [J]. Biomacromolecules, 2012, 13(6):1956-1964. [55] Yao Xinpeng, Liu Yi, Gao Jie, et al. Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction. Biomaterials, 2015, 60:130-140. [56] Chierchia A, Chirico N, Boeri L, et al. Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson′s disease related toxin 6-hydroxydopamine [J]. Eur J Pharm Biopharm, 2017, 121:113-120. [57] Moussa L, Pattappa G, Doix B, et al. A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic radiation-induced damage [J]. Biomaterials, 2017, 115:40-52. [58] Cho SH, Noh JR, Cho MY, et al. An injectable collagen/poly (γ-glutamic acid) hydrogel as a scaffold of stem cells and α-lipoic acid for enhanced protection against renal dysfunction [J]. Biomater Sci, 2017, 5(2):285-294. [59] Bal T, Nazli C, Okcu A, et al. Mesenchymal stem cells and ligand incorporation in biomimetic poly (ethylene glycol) hydrogels significantly improve insulin secretion from pancreatic islets [J]. J Tissue Eng Regen Med, 2017, 11(3):694-703. [60] Mohammadi Ayenehdeh J, Niknam B, Rasouli S, et al. Immunomodulatory and protective effects of adipose tissue-derived mesenchymal stem cells in an allograft islet composite transplantation for experimental autoimmune type 1 diabetes [J]. Immunol Lett, 2017, 188:21-31. [61] Park YB, Ha CW, Kim JA, et al. Effect of transplanting various concentrations of a composite of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel on articular cartilage repair in a rabbit model [J]. PLoS ONE, 2016, 11(11):e0165446. [62] Cai Min, Shen Rui, Song Lei. et al. Bone marrow mesenchymal stem cells (BM-MSCs) improve heart function in swine myocardial infarction model through paracrine effects [J]. Sci Rep, 2016, 6:1-11. [63] Wang Feng, Guan Jianjun. Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy [J]. Adv Drug Deliv Rev, 2010, 62(7-8):784-97. [64] Tseng TC, Lei Tao, Hsieh FY, et al. An Injectable, self-healing hydrogel to repair the central nervous system [J]. Adv Mater, 2015, 27(23):3518-3524.
