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Current Chinese Science

Editor-in-Chief

ISSN (Print): 2210-2981
ISSN (Online): 2210-2914

Clinical Trial Section: Biomaterials

Efficacious Restoration of Intractable Trauma by Administration of Mesenchymal Stem/Stromal Cells and Hydrogel Composite: A Case Series

Author(s): Leisheng Zhang* and Zhongchao Han

Volume 3, Issue 2, 2023

Published on: 11 January, 2023

Page: [106 - 116] Pages: 11

DOI: 10.2174/2210298103666221228143135

Price: $65

Abstract

Background and Objectives: Patients with intractable cutaneous injuries and complications such as severe ulcers and dysfunctions often result in unfavorable prognosis and burdensome possessions esthetically and psychosocially. This study aimed to evaluate the preliminary safety and efficacy outcomes of hyaluronic acid/placenta-derived mesenchymal stem/stromal cells (HA/P-MSCs) composite upon extensive traumas.

Methods: The phase Ⅰ of the interventional study with four enrolled patients with refractory wounds and ulcerations was conducted. With the consent of the patients and approval of the ethics committee, continuous HA/P-MSC composite administration was conducted on the surface of wounds after surgical debridement. The dynamic changes in pathomorphology and therapeutic response were collectively recorded.

Results: All the participants revealed efficacious remission with clinical-grade HA/P-MSC composite, including complete wound healing, elimination of inflammatory exudate and refractory ulcers, and regeneration of damaged tissues under sterile conditions. No untoward effects or recurrence were observed in the cases during treatment and the 24-month’s follow-up visit.

Conclusion: Refractory wound management with HA/P-MSC composite was preliminarily safe and effective for the improvement of the outcomes of the patients. These findings provided new references for the treatment of the costliest and incurable diseases associated with cutaneous injuries.

Keywords: Placenta-derived MSCs, hyaluronic acid, intractable trauma, cutaneous ulcer, efficacious remission, case series.

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[1]
Sun, B.K.; Siprashvili, Z.; Khavari, P.A. Advances in skin grafting and treatment of cutaneous wounds. Science, 2014, 346(6212), 941-945.
[http://dx.doi.org/10.1126/science.1253836] [PMID: 25414301]
[2]
Krishnaswamy, V.R.; Mintz, D.; Sagi, I. Matrix metalloproteinases: The sculptors of chronic cutaneous wounds. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(11 Pt B), 2220-2227.
[http://dx.doi.org/10.1016/j.bbamcr.2017.08.003] [PMID: 28797647]
[3]
Hall, C.; Hardin, C.; Corkins, C.J.; Jiwani, A.Z.; Fletcher, J.; Carlsson, A.; Chan, R. Pathophysiologic mechanisms and current treatments for cutaneous sequelae of burn wounds. Compr. Physiol., 2017, 8(1), 371-405.
[http://dx.doi.org/10.1002/cphy.c170016] [PMID: 29357133]
[4]
Hu, C.H.; Tseng, Y.W.; Chiou, C.Y.; Lan, K.C.; Chou, C.H.; Tai, C.S.; Huang, H.D.; Hu, C.W.; Liao, K.H.; Chuang, S.S.; Yang, J.Y.; Lee, O.K. Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model. Stem Cell Res. Ther., 2019, 10(1), 275.
[http://dx.doi.org/10.1186/s13287-019-1383-x] [PMID: 31462299]
[5]
Fu, X. Wound healing center establishment and new technology application in improving the wound healing quality in China. Burns Trauma, 2020, 8, tkaa038.
[http://dx.doi.org/10.1093/burnst/tkaa038] [PMID: 33134399]
[6]
L, P.K.; Kandoi, S.; Misra, R.; S, V.; K, R.; Verma, R.S. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev., 2019, 46, 1-9.
[http://dx.doi.org/10.1016/j.cytogfr.2019.04.002] [PMID: 30954374]
[7]
Zhao, Q.; Zhang, L.; Wei, Y.; Yu, H.; Zou, L.; Huo, J.; Yang, H.; Song, B.; Wei, T.; Wu, D.; Zhang, W.; Zhang, L.; Liu, D.; Li, Z.; Chi, Y.; Han, Z.; Han, Z. Systematic comparison of hUC-MSCs at various passages reveals the variations of signatures and therapeutic effect on acute graft-versus-host disease. Stem Cell Res. Ther., 2019, 10(1), 354.
[http://dx.doi.org/10.1186/s13287-019-1478-4] [PMID: 31779707]
[8]
Wang, L.; Zhang, L.; Liang, X.; Zou, J.; Liu, N.; Liu, T.; Wang, G.; Ding, X.; Liu, Y.; Zhang, B.; Liang, R.; Wang, S. Adipose tissue-derived stem cells from type 2 diabetics reveal conservative alterations in multidimensional characteristics. Int. J. Stem Cells, 2020, 13(2), 268-278.
[http://dx.doi.org/10.15283/ijsc20028] [PMID: 32587133]
[9]
Hocking, A.M. Mesenchymal stem cell therapy for cutaneous wounds. Adv. Wound Care, 2012, 1(4), 166-171.
[http://dx.doi.org/10.1089/wound.2011.0294] [PMID: 24527299]
[10]
Liu, W.; Yu, M.; Xie, D.; Wang, L.; Ye, C.; Zhu, Q.; Liu, F.; Yang, L. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res. Ther., 2020, 11(1), 259.
[http://dx.doi.org/10.1186/s13287-020-01756-x] [PMID: 32600435]
[11]
Guillamat-Prats, R. The role of msc in wound healing, scarring and regeneration. Cells, 2021, 10(7), 1729.
[http://dx.doi.org/10.3390/cells10071729] [PMID: 34359898]
[12]
Fan, D.; Zeng, M.; Xia, Q.; Wu, S.; Ye, S.; Rao, J.; Lin, D.; Zhang, H.; Ma, H.; Han, Z.; Guo, X.; Liu, Z. Efficacy and safety of umbilical cord mesenchymal stem cells in treatment of cesarean section skin scars: A randomized clinical trial. Stem Cell Res. Ther., 2020, 11(1), 244.
[http://dx.doi.org/10.1186/s13287-020-01695-7] [PMID: 32586366]
[13]
Fan, D.; Xia, Q.; Wu, S.; Ye, S.; Liu, L.; Wang, W.; Guo, X.; Liu, Z. Mesenchymal stem cells in the treatment of cesarean section skin scars: Study protocol for a randomized, controlled trial. Trials, 2018, 19(1), 155.
[http://dx.doi.org/10.1186/s13063-018-2478-x] [PMID: 29499740]
[14]
Li, L.; Zhang, Y.; Mu, J.; Chen, J.; Zhang, C.; Cao, H.; Gao, J. Transplantation of human mesenchymal stem-cell-derived exosomes immobilized in an adhesive hydrogel for effective treatment of spinal cord injury. Nano Lett., 2020, 20(6), 4298-4305.
[http://dx.doi.org/10.1021/acs.nanolett.0c00929] [PMID: 32379461]
[15]
Zhang, L.; Wei, Y.; Chi, Y.; Liu, D.; Yang, S.; Han, Z.; Li, Z. Two-step generation of mesenchymal stem/stromal cells from human pluripotent stem cells with reinforced efficacy upon osteoarthritis rabbits by HA hydrogel. Cell Biosci., 2021, 11(1), 6.
[http://dx.doi.org/10.1186/s13578-020-00516-x] [PMID: 33407870]
[16]
Ji, X.; Yuan, X.; Ma, L.; Bi, B.; Zhu, H.; Lei, Z.; Liu, W.; Pu, H.; Jiang, J.; Jiang, X.; Zhang, Y.; Xiao, J. Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(ε-caprolactone)/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation. Theranostics, 2020, 10(2), 725-740.
[http://dx.doi.org/10.7150/thno.39167] [PMID: 31903147]
[17]
Khayambashi, P.; Iyer, J.; Pillai, S.; Upadhyay, A.; Zhang, Y.; Tran, S. Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering. Int. J. Mol. Sci., 2021, 22(2), 684.
[http://dx.doi.org/10.3390/ijms22020684] [PMID: 33445616]
[18]
Zeng, X.; Tang, Y.; Hu, K.; Jiao, W.; Ying, L.; Zhu, L.; Liu, J.; Xu, J. Three-week topical treatment with placenta-derived mesenchymal stem cells hydrogel in a patient with diabetic foot ulcer. Medicine, 2017, 96(51), e9212.
[http://dx.doi.org/10.1097/MD.0000000000009212] [PMID: 29390468]
[19]
Hou, H.; Zhang, L.; Duan, L.; Liu, Y.; Han, Z.; Li, Z.; Cao, X. Spatio-temporal metabolokinetics and efficacy of human placenta-derived mesenchymal stem/stromal cells on mice with refractory crohn’s-like enterocutaneous fistula. Stem Cell Rev. Rep., 2020, 16(6), 1292-1304.
[http://dx.doi.org/10.1007/s12015-020-10053-2] [PMID: 33011925]
[20]
Saleh, M.; Taher, M.; Sohrabpour, A.A.; Vaezi, A.A.; Nasiri Toosi, M.; Kavianpour, M.; Ghazvinian, Z.; Abdolahi, S.; Verdi, J. Perspective of placenta derived mesenchymal stem cells in acute liver failure. Cell Biosci., 2020, 10(1), 71.
[http://dx.doi.org/10.1186/s13578-020-00433-z] [PMID: 32483484]
[21]
Nombela-Arrieta, C.; Ritz, J.; Silberstein, L.E. The elusive nature and function of mesenchymal stem cells. Nat. Rev. Mol. Cell Biol., 2011, 12(2), 126-131.
[http://dx.doi.org/10.1038/nrm3049] [PMID: 21253000]
[22]
Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.C.; Krause, D.S.; Deans, R.J.; Keating, A.; Prockop, D.J.; Horwitz, E.M. Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement. Cytotherapy, 2006, 8(4), 315-317.
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[23]
Kennedy, A.; Van Zant, R.S. Diverse applications of negative pressure wound therapy: A multiple case report. Physiother. Theory Pract., 2006, 22(2), 83-90.
[http://dx.doi.org/10.1080/09593980600588781] [PMID: 16703817]
[24]
Shah, A.; Wollak, C.; Shah, J.B. Wound measurement techniques: Comparing the use of ruler method, 2d imaging and 3d scanner. J. Am. Coll. Clin. Wound Spec., 2013, 5(3), 52-57.
[http://dx.doi.org/10.1016/j.jccw.2015.02.001] [PMID: 26199893]
[25]
Zhang, X.; Yang, Y.; Zhang, L.; Lu, Y.; Zhang, Q.; Fan, D.; Zhang, Y.; Zhang, Y.; Ye, Z.; Xiong, D. Mesenchymal stromal cells as vehicles of tetravalent bispecific tandab (CD3/CD19) for the treatment of B cell lymphoma combined with IDO pathway inhibitor d-1-methyl-tryptophan. J. Hematol. Oncol., 2017, 10(1), 56.
[http://dx.doi.org/10.1186/s13045-017-0397-z] [PMID: 28228105]
[26]
Zhang, L.; Liu, C.; Wang, H.; Wu, D.; Su, P.; Wang, M.; Guo, J.; Zhao, S.; Dong, S.; Zhou, W.; Arakaki, C.; Zhang, X.; Zhou, J. Thrombopoietin knock-in augments platelet generation from human embryonic stem cells. Stem Cell Res. Ther., 2018, 9(1), 194.
[http://dx.doi.org/10.1186/s13287-018-0926-x] [PMID: 30016991]
[27]
Zhang, W.; Liu, C.; Wu, D.; Liang, C.; Zhang, L.; Zhang, Q.; Liu, Y.; Xia, M.; Wang, H.; Su, P.; Feng, S.; Han, M.; Zhou, J.; Wang, F.; Jiang, E. Decitabine improves platelet recovery by down-regulating IL-8 level in MDS/AML patients with thrombocytopenia. Blood Cells Mol. Dis., 2019, 76, 66-71.
[http://dx.doi.org/10.1016/j.bcmd.2019.02.003] [PMID: 30846359]
[28]
Wu, Q.; Zhang, L.; Su, P.; Lei, X.; Liu, X.; Wang, H.; Lu, L.; Bai, Y.; Xiong, T.; Li, D.; Zhu, Z.; Duan, E.; Jiang, E.; Feng, S.; Han, M.; Xu, Y.; Wang, F.; Zhou, J. MSX2 mediates entry of human pluripotent stem cells into mesendoderm by simultaneously suppressing SOX2 and activating NODAL signaling. Cell Res., 2015, 25(12), 1314-1332.
[http://dx.doi.org/10.1038/cr.2015.118] [PMID: 26427715]
[29]
LeBlanc, K.; Langemo, D.; Woo, K.; Campos, H.M.H.; Santos, V. Holloway, S Skin tears: Prevention and management. Br. J. Community Nurs., 2019, 24(S9), S12-S18.
[http://dx.doi.org/10.12968/bjcn.2019.24.Sup9.S12]
[30]
Maranda, E.; Rodriguez-Menocal, L.; Badiavas, E. Role of mesenchymal stem cells in dermal repair in burns and diabetic wounds. Curr. Stem Cell Res. Ther., 2016, 12(1), 61-70.
[http://dx.doi.org/10.2174/1574888X11666160714115926] [PMID: 27412677]
[31]
Zhang, L.; Wang, H.; Liu, C.; Wu, Q.; Su, P.; Wu, D.; Guo, J.; Zhou, W.; Xu, Y.; Shi, L.; Zhou, J. MSX2 Initiates and accelerates mesenchymal stem/stromal cell specification of hpscs by regulating TWIST1 and PRAME. Stem Cell Reports, 2018, 11(2), 497-513.
[http://dx.doi.org/10.1016/j.stemcr.2018.06.019] [PMID: 30033084]
[32]
Kim, Y.; Jin, H.J.; Heo, J.; Ju, H.; Lee, H.Y.; Kim, S.; Lee, S.; Lim, J.; Jeong, S.Y.; Kwon, J.; Kim, M.; Choi, S.J.; Oh, W.; Yang, Y.S.; Hwang, H.H.; Yu, H.Y.; Ryu, C.M.; Jeon, H.B.; Shin, D.M. Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease. Leukemia, 2018, 32(12), 2672-2684.
[http://dx.doi.org/10.1038/s41375-018-0151-8] [PMID: 29789652]
[33]
Ding, L.; Yan, G.; Wang, B.; Xu, L.; Gu, Y.; Ru, T.; Cui, X.; Lei, L.; Liu, J.; Sheng, X.; Wang, B.; Zhang, C.; Yang, Y.; Jiang, R.; Zhou, J.; Kong, N.; Lu, F.; Zhou, H.; Zhao, Y.; Chen, B.; Hu, Y.; Dai, J.; Sun, H. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility. Sci. China Life Sci., 2018, 61(12), 1554-1565.
[http://dx.doi.org/10.1007/s11427-017-9272-2] [PMID: 29546669]
[34]
Fan, X.; Gay, F.P.H.; Ong, S.Y.; Ang, J.M.L.; Chu, P.P.Y.; Bari, S.; Lim, T.K.H.; Hwang, W.Y.K. Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease. Cytotherapy, 2013, 15(5), 610-619.
[http://dx.doi.org/10.1016/j.jcyt.2012.12.007] [PMID: 23419678]
[35]
Yao, J.; Chen, N.; Wang, X.; Zhang, L.; Huo, J.; Chi, Y.; Li, Z.; Han, Z. Human supernumerary teeth-derived apical papillary stem cells possess preferable characteristics and efficacy on hepatic fibrosis in mice. Stem Cells Int., 2020, 2020, 1-12.
[http://dx.doi.org/10.1155/2020/6489396] [PMID: 32399047]
[36]
Kern, S.; Eichler, H.; Stoeve, J.; Klüter, H.; Bieback, K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 2006, 24(5), 1294-1301.
[http://dx.doi.org/10.1634/stemcells.2005-0342] [PMID: 16410387]
[37]
Wei, Y.; Hou, H.; Zhang, L.; Zhao, N.; Li, C.; Huo, J.; Liu, Y.; Zhang, W.; Li, Z.; Liu, D.; Han, Z.; Zhang, L.; Song, B.; Chi, Y.; Han, Z. JNKi- and DAC-programmed mesenchymal stem/stromal cells from hESCs facilitate hematopoiesis and alleviate hind limb ischemia. Stem Cell Res. Ther., 2019, 10(1), 186.
[http://dx.doi.org/10.1186/s13287-019-1302-1] [PMID: 31234947]
[38]
Jiang, B.; Yan, L.; Wang, X.; Li, E.; Murphy, K.; Vaccaro, K.; Li, Y.; Xu, R.H. Concise review: Mesenchymal stem cells derived from human pluripotent cells, an unlimited and quality-controllable source for therapeutic applications. Stem Cells, 2019, 37(5), 572-581.
[http://dx.doi.org/10.1002/stem.2964] [PMID: 30561809]
[39]
Du, W.; Li, X.; Chi, Y.; Ma, F.; Li, Z.; Yang, S.; Song, B.; Cui, J.; Ma, T.; Li, J.; Tian, J.; Yang, Z.; Feng, X.; Chen, F.; Lu, S.; Liang, L.; Han, Z.B.; Han, Z.C. VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity. Stem Cell Res. Ther., 2016, 7(1), 49.
[http://dx.doi.org/10.1186/s13287-016-0297-0] [PMID: 27044487]
[40]
Wei, Y.; Zhang, L.; Chi, Y.; Ren, X.; Gao, Y.; Song, B.; Li, C.; Han, Z.; Zhang, L.; Han, Z. High‐efficient generation of VCAM‐1 + mesenchymal stem cells with multidimensional superiorities in signatures and efficacy on aplastic anaemia mice. Cell Prolif., 2020, 53(8), e12862.
[http://dx.doi.org/10.1111/cpr.12862] [PMID: 32597552]
[41]
Akyurekli, C.; Le, Y.; Richardson, R.B.; Fergusson, D.; Tay, J.; Allan, D.S. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev., 2015, 11(1), 150-160.
[http://dx.doi.org/10.1007/s12015-014-9545-9] [PMID: 25091427]
[42]
Matthay, M.A.; Pati, S.; Lee, J.W. Concise review: Mesenchymal stem (Stromal) cells: Biology and preclinical evidence for therapeutic potential for organ dysfunction following trauma or sepsis. Stem Cells, 2017, 35(2), 316-324.
[http://dx.doi.org/10.1002/stem.2551] [PMID: 27888550]
[43]
Casado-Díaz, A.; Quesada-Gómez, J.M.; Dorado, G. Extracellular vesicles derived from mesenchymal stem cells (msc) in regenerative medicine: Applications in skin wound healing. Front. Bioeng. Biotechnol., 2020, 8, 146.
[http://dx.doi.org/10.3389/fbioe.2020.00146] [PMID: 32195233]
[44]
Li, B.; Luan, S.; Chen, J.; Zhou, Y.; Wang, T.; Li, Z.; Fu, Y.; Zhai, A.; Bi, C. The msc-derived exosomal lncrna h19 promotes wound healing in diabetic foot ulcers by upregulating pten via microRNA-152-3p. Mol. Ther. Nucleic Acids, 2020, 19, 814-826.
[http://dx.doi.org/10.1016/j.omtn.2019.11.034] [PMID: 31958697]
[45]
Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; Xu, W. Hucmsc-exosome mediated-wnt4 signaling is required for cutaneous wound healing. Stem Cells, 2015, 33(7), 2158-2168.
[http://dx.doi.org/10.1002/stem.1771] [PMID: 24964196]
[46]
Zhang, J.; Guan, J.; Niu, X.; Hu, G.; Guo, S.; Li, Q.; Xie, Z.; Zhang, C.; Wang, Y. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J. Transl. Med., 2015, 13(1), 49.
[http://dx.doi.org/10.1186/s12967-015-0417-0] [PMID: 25638205]
[47]
Yu, M.; Liu, W.; Li, J.; Lu, J.; Lu, H.; Jia, W.; Liu, F. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res. Ther., 2020, 11(1), 350.
[http://dx.doi.org/10.1186/s13287-020-01824-2] [PMID: 32787917]
[48]
Pajarinen, J.; Lin, T.; Gibon, E.; Kohno, Y.; Maruyama, M.; Nathan, K.; Lu, L.; Yao, Z.; Goodman, S.B. Mesenchymal stem cell-macrophage crosstalk and bone healing. Biomaterials, 2019, 196, 80-89.
[http://dx.doi.org/10.1016/j.biomaterials.2017.12.025] [PMID: 29329642]
[49]
Brennan, M.Á.; Layrolle, P.; Mooney, D.J. Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv. Funct. Mater., 2020, 30(37), 1909125.
[http://dx.doi.org/10.1002/adfm.201909125] [PMID: 32952493]
[50]
Yang, J.; Chen, Z.; Pan, D.; Li, H.; Shen, J. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic f127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. Int. J. Nanomedicine, 2020, 15, 5911-5926.
[http://dx.doi.org/10.2147/IJN.S249129] [PMID: 32848396]

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