Platelet poor plasma gel combined with amnion improves the therapeutic effects of human umbilical cord‑derived mesenchymal stem cells on wound healing in rats

Yang,Lujun; Ma,Jie; Gan,Saiyang; Chu,Shuli; Maldonado,Martin; Zhou,Jianda; Ma,Lian; Tang,Shijie

doi:10.3892/mmr.2017.6961

Platelet poor plasma gel combined with amnion improves the therapeutic effects of human umbilical cord‑derived mesenchymal stem cells on wound healing in rats

Authors:
- Lujun Yang
- Jie Ma
- Saiyang Gan
- Shuli Chu
- Martin Maldonado
- Jianda Zhou
- Lian Ma
- Shijie Tang
View Affiliations

Affiliations: Department of Burns and Plastic Surgery, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Research Center for Translational Medicine, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: July 13, 2017 https://doi.org/10.3892/mmr.2017.6961
Pages: 3494-3502

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the efficacy of human umbilical cord‑derived mesenchymal stem cell (HUMSCs) embedded in platelet poor plasma (PPP) gel combined with amnion (PPPA) in improving wound healing on Sprague‑Dawley (SD) rats. HUMSCs were cultured and labeled with chloromethylbenzamido‑1,1'‑dioctadecyl‑3,3,3'3'‑tetramethylindocarbocyanine perchlorate (CM‑DiI) on their third passage. The expression levels of growth factors of HUMSCs in PPPA were assessed by ELISA. Full‑thickness excisional skin wounds were induced in 36 male SD rats, which were treated with PPPA grafted with HUMSCs (PPPAC), PPPA, or HUMSC or PBS injection. The degree of healing and the distribution of labeled HUMSCs in the wound were evaluated by hematoxylin and eosin (H&E) staining and immunofluorescence. On day 14 post‑surgery, wound healing in PPPAC‑treated rats was significantly higher than the PPPA group, compared with rats treated with HUMSCs alone and control rats (P<0.05 and P<0.01, respectively). H&E staining showed that morphology and thickness of the epidermis in the PPPAC group was similar to that of healthy skin. ELISA revealed that levels of growth factors of HUMSCs in PPPAC were higher than in monolayer cells. In conclusion, PPPA can modify growth factor expression levels of HUMSCs and improve the efficiency of HUMSCs in the healing of full thickness wounds in rats.

View Figures

View References

1	Atiyeh BS, Gunn SW and Hayek SN: State of the art in burn treatment. World J Surg. 29:131–148. 2005. View Article : Google Scholar : PubMed/NCBI
2	Hocking AM and Gibran NS: Mesenchymal stem cells: Paracrine signaling and differentiation during cutaneous wound repair. Exp Cell Res. 316:2213–2219. 2010. View Article : Google Scholar : PubMed/NCBI
3	Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 276:71–74. 1997. View Article : Google Scholar : PubMed/NCBI
4	da Silva Meirelles L, Chagastelles PC and Nardi NB: Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 119:2204–2213. 2006. View Article : Google Scholar : PubMed/NCBI
5	Bongso A and Fong CY: The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton's jelly of the human umbilical cord. Stem Cell Rev. 9:226–240. 2013. View Article : Google Scholar : PubMed/NCBI
6	Jadalannagari S and Aljitawi OS: Ectodermal Differentiation of wharton's jelly mesenchymal stem cells for tissue engineering and regenerative medicine applications. Tissue Eng Part B Rev. 21:314–322. 2015. View Article : Google Scholar : PubMed/NCBI
7	Zhao G, Liu F, Lan S, Li P, Wang L, Kou J, Qi X, Fan R, Hao D, Wu C, et al: Large-scale expansion of Wharton's jelly-derived mesenchymal stem cells on gelatin microbeads, with retention of self-renewal and multipotency characteristics and the capacity for enhancing skin wound healing. Stem Cell Res Ther. 6:382015. View Article : Google Scholar : PubMed/NCBI
8	Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A, et al: International Society for Cellular Therapy: Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 7:393–395. 2005. View Article : Google Scholar : PubMed/NCBI
9	Tang Q, Chen Q, Lai X, Liu S, Chen Y, Zheng Z, Xie Q, Maldonado M, Cai Z, Qin S, et al: Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction. PLoS One. 8:e818442013. View Article : Google Scholar : PubMed/NCBI
10	Hanson SE, Bentz ML and Hematti P: Mesenchymal stem cell therapy for nonhealing cutaneous wounds. Plast Reconstr Surg. 125:510–516. 2010. View Article : Google Scholar : PubMed/NCBI
11	Balaji S, Keswani SG and Crombleholme TM: The role of mesenchymal stem cells in the regenerative wound healing phenotype. Adv Wound Care (New Rochelle). 1:159–165. 2012. View Article : Google Scholar : PubMed/NCBI
12	Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D and Shimizu H: Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol. 180:2581–2587. 2008. View Article : Google Scholar : PubMed/NCBI
13	Khosrotehrani K: Mesenchymal stem cell therapy in skin: Why and what for? Exp Dermatol. 22:307–310. 2013. View Article : Google Scholar : PubMed/NCBI
14	Arno AI, Amini-Nik S, Blit PH, Al-Shehab M, Belo C, Herer E, Tien CH and Jeschke MG: Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling. Stem Cell Res Ther. 5:282014. View Article : Google Scholar : PubMed/NCBI
15	Huang P, Lin LM, Wu XY, Tang QL, Feng XY, Lin GY, Lin X, Wang HW, Huang TH and Ma L: Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells into germ-like cells in vitro. J Cell Biochem. 109:747–754. 2010.PubMed/NCBI
16	Weir C, Morel-Kopp MC, Gill A, Tinworth K, Ladd L, Hunyor SN and Ward C: Mesenchymal stem cells: Isolation, characterisation and in vivo fluorescent dye tracking. Heart Lung Circ. 17:395–403. 2008. View Article : Google Scholar : PubMed/NCBI
17	Hemmrich K, Meersch M, von Heimburg D and Pallua N: Applicability of the dyes CFSE, CM-DiI and PKH26 for tracking of human preadipocytes to evaluate adipose tissue engineering. Cells Tissues Organs. 184:117–127. 2006. View Article : Google Scholar : PubMed/NCBI
18	Yang L, Shirakata Y, Shudou M, Dai X, Tokumaru S, Hirakawa S, Sayama K, Hamuro J and Hashimoto K: New skin-equivalent model from de-epithelialized amnion membrane. Cell Tissue Res. 326:69–77. 2006. View Article : Google Scholar : PubMed/NCBI
19	Woo SH, Kim JP, Park JJ, Chung PS, Lee SH and Jeong HS: Autologous platelet-poor plasma gel for injection laryngoplasty. Yonsei Med J. 54:1516–1523. 2013. View Article : Google Scholar : PubMed/NCBI
20	Chen L, Tredget EE, Wu PY and Wu Y: Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. 3:e18862008. View Article : Google Scholar : PubMed/NCBI
21	Galiano RD, Michaels J 5th, Dobryansky M, Levine JP and Gurtner GC: Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen. 12:485–492. 2004. View Article : Google Scholar : PubMed/NCBI
22	Hussain I, Magd SA, Eremin O and El-Sheemy M: New approach to isolate mesenchymal stem cell (MSC) from human umbilical cord blood. Cell Biol Int. 36:595–600. 2012. View Article : Google Scholar : PubMed/NCBI
23	Park SE, Jung NY, Lee NK, Lee J, Hyung B, Myeong SH, Kim HS, Suh YL, Lee JI, Cho KR, et al: Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in canines after intracerebroventricular injection. Neurobiol Aging. 47:192–200. 2016. View Article : Google Scholar : PubMed/NCBI
24	Ding Y, Yang H, Feng JB, Qiu Y, Li DS and Zeng Y: Human umbilical cord-derived MSC culture: The replacement of animal sera with human cord blood plasma. In Vitro Cell Dev Biol Anim. 49:771–777. 2013. View Article : Google Scholar : PubMed/NCBI
25	Secco M, Zucconi E, Vieira NM, Fogaca LL, Cerqueira A, Carvalho MD, Jazedje T, Okamoto OK, Muotri AR and Zatz M: Multipotent stem cells from umbilical cord: Cord is richer than blood! Stem Cells. 26:146–150. 2008. View Article : Google Scholar : PubMed/NCBI
26	Ma L, Feng XY, Cui BL, Law F, Jiang XW, Yang LY, Xie QD and Huang TH: Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells. Chin Med J (Engl). 118:1987–1993. 2005.PubMed/NCBI
27	Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D and Can A: Biology of stem cells in human umbilical cord stroma: In situ and in vitro surveys. Stem Cells. 25:319–331. 2007. View Article : Google Scholar : PubMed/NCBI
28	MacKenzie TC and Flake AW: Human mesenchymal stem cells: Insights from a surrogate in vivo assay system. Cells Tissues Organs. 171:90–95. 2002. View Article : Google Scholar : PubMed/NCBI
29	Song H, Song BW, Cha MJ, Choi IG and Hwang KC: Modification of mesenchymal stem cells for cardiac regeneration. Expert Opin Biol Ther. 10:309–319. 2010. View Article : Google Scholar : PubMed/NCBI
30	Leontieva OV, Demidenko ZN and Blagosklonny MV: Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proc Natl Acad Sci USA. 111:8832–8837. 2014. View Article : Google Scholar : PubMed/NCBI
31	Hayes CS, Koskiniemi S, Ruhe ZC, Poole SJ and Low DA: Mechanisms and biological roles of contact-dependent growth inhibition systems. Cold Spring Harb Perspect Med. 4:pii: a010025. 2014. View Article : Google Scholar : PubMed/NCBI
32	Reiser J, Zhang XY, Hemenway CS, Mondal D, Pradhan L and La Russa VF: Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases. Expert Opin Biol Ther. 5:1571–1584. 2005. View Article : Google Scholar : PubMed/NCBI
33	Michel M, L'Heureux N, Pouliot R, Xu W, Auger FA and Germain L: Characterization of a new tissue-engineered human skin equivalent with hair. In Vitro Cell Dev Biol Anim. 35:318–326. 1999. View Article : Google Scholar : PubMed/NCBI
34	Nita AC, Orzan OA, Filipescu M and Jianu D: Fat graft, laser CO₂ and platelet-rich-plasma synergy in scars treatment. J Med Life. 6:430–433. 2013.PubMed/NCBI
35	Kawazoe T and Kim HH: Tissue augmentation by white blood cell-containing platelet-rich plasma. Cell Transplant. 21:601–607. 2012. View Article : Google Scholar : PubMed/NCBI
36	Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, do Corrêa Amaral RJ, Granjeiro JM and Borojevic R: Platelet-rich plasma preparation for regenerative medicine: Optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 4:672013. View Article : Google Scholar : PubMed/NCBI
37	Diamond SL: Systems biology of coagulation. J Thromb Haemost. 11:(Suppl 1). S224–S232. 2013. View Article : Google Scholar
38	Sierra DH: Fibrin sealant adhesive systems: A review of their chemistry, material properties and clinical applications. J Biomater Appl. 7:309–352. 1993. View Article : Google Scholar : PubMed/NCBI
39	Malafaya PB, Silva GA and Reis RL: Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev. 59:207–233. 2007. View Article : Google Scholar : PubMed/NCBI
40	Insausti CL, Alcaraz A, García-Vizcaíno EM, Mrowiec A, López-Martínez MC, Blanquer M, Piñero A, Majado MJ, Moraleda JM, Castellanos G and Nicolás FJ: Amniotic membrane induces epithelialization in massive posttraumatic wounds. Wound Repair Regen. 18:368–377. 2010. View Article : Google Scholar : PubMed/NCBI
41	Gurtner GC, Werner S, Barrandon Y and Longaker MT: Wound repair and regeneration. Nature. 453:314–321. 2008. View Article : Google Scholar : PubMed/NCBI