Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway

被引：71

作者：

Ebrahim, Nesrine ^{[1
,2
]}

Dessouky, Arigue A. ^{[3
]}

Mostafa, Ola ^{[1
]}

Hassouna, Amira ^{[4
]}

Yousef, Mohamed M. ^{[1
]}

Seleem, Yasmin ^{[5
]}

El Gebaly, Eman Abd El Aziz M. ^{[5
]}

Allam, Mona M. ^{[6
]}

Farid, Ayman Samir ^{[7
]}

Saffaf, Bayan A. ^{[8
]}

Sabry, Dina ^{[9
,10
]}

Nawar, Ahmed ^{[11
]}

Shoulah, Ahmed A. ^{[11
]}

Khalil, Ahmed H. ^{[12
]}

Abdalla, Sami F. ^{[13
]}

El-Sherbiny, Mohamed ^{[14
]}

Elsherbiny, Nehal M. ^{[15
,16
]}

Salim, Rabab F. ^{[17
,18
]}

机构：

[1] Benha Univ, Fac Med, Dept Histol & Cell Biol, Banha, Egypt

[2] Benha Univ, Fac Med, Stem Cell Unit, Banha, Egypt

[3] Zagazig Univ, Fac Med, Dept Histol & Cell Biol, Zagazig, Egypt

[4] AUT Univ, Fac Hlth & Environm Sci, Sch Interprofess Hlth Studies, Auckland, New Zealand

[5] Benha Univ, Fac Med, Dept Clin Pharmacol, Banha, Egypt

[6] Benha Univ, Fac Med, Dept Med Physiol, Banha, Egypt

[7] Benha Univ Moshtohor, Fac Vet Med, Dept Clin Pathol, Toukh 13736, Egypt

[8] Future Univ, Fac Pharm, Dept Pharm, New Cairo, Egypt

[9] Cairo Univ, Fac Med, Dept Med Biochem & Mol Biol, Cairo, Egypt

[10] Badr Univ, Fac Med, Dept Med Biochem & Mol Biol, Cairo 11562, Egypt

[11] Benha Univ, Fac Med, Dept Gen Surg, Banha, Egypt

[12] Benha Univ, Fac Vet Med, Dept Surg & Radiol, Banha, Egypt

[13] AlMaarefa Univ, Coll Med, Clin Dept, Riyadh, Saudi Arabia

[14] AlMaarefa Univ, Coll Med, Dept Basic Med Sci, Riyadh, Saudi Arabia

[15] Mansoura Univ, Fac Med, Dept Anat, Mansoura, Egypt

[16] Mansoura Univ, Fac Pharm, Dept Biochem, Mansoura 35516, Egypt

[17] Univ Tabuk, Fac Pharm, Dept Pharmaceut Chem, Tabuk, Saudi Arabia

[18] Benha Univ, Fac Med, Dept Med Biochem & Mol Biol, Banha, Egypt

来源：

STEM CELL RESEARCH & THERAPY | 2021年 / 12卷 / 01期

关键词：

Diabetic wound; Adipose mesenchymal stem cells; PRP; Notch pathway; STROMAL-VASCULAR FRACTION; ENDOTHELIAL PROGENITOR CELLS; LIGAND DELTA-LIKE-4; DIFFERENTIATION; ANGIOGENESIS; EXPRESSION; TRANSPLANTATION; PROLIFERATION; GROWTH; CXCR4;

D O I：

10.1186/s13287-021-02454-y

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. Methods Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ss1 Integrin) were assessed. Results Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. Conclusions These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.

引用

页数：24

共 102 条

[1] Long term conjugated linoleic acid supplementation modestly improved growth performance but induced testicular tissue apoptosis and reduced sperm quality in male rabbit [J].

Abdelatty, A. M. ;

Badr, O. A. M. ;

Mohamed, S. A. ;

Khattab, M. S. ;

Dessouki, Sh. M. ;

Farid, O. A. A. ;

Elolimy, A. A. ;

Sakr, O. G. ;

Elhady, M. A. ;

Mehesen, G. ;

Bionaz, M. .

PLOS ONE, 2020, 15 (01)

[2] Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective [J].

Akil, Abdellah ;

Gutierrez-Garcia, Ana K. ;

Guenter, Rachael ;

Rose, J. Bart ;

Beck, Adam W. ;

Chen, Herbert ;

Ren, Bin .

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9

[3]

[Anonymous], 2020, INT J MOL SCI

[4] The potent therapeutic effect of novel cyanobacterial isolates against oxidative stress damage in redox rats [J].

Badr, O. A. M. ;

EL-Shawaf, I. I. S. ;

El-Garhy, H. A. S. ;

Moustafa, M. M. A. ;

Ahmed-Farid, O. A. .

JOURNAL OF APPLIED MICROBIOLOGY, 2019, 126 (04) :1278-1289

[5] Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species [J].

Baglio, Serena Rubina ;

Rooijers, Koos ;

Koppers-Lalic, Danijela ;

Verweij, Frederik J. ;

Lanzon, M. Perez ;

Zini, Nicoletta ;

Naaijkens, Benno ;

Perut, Francesca ;

Niessen, Hans W. M. ;

Baldini, Nicola ;

Pegtel, D. Michiel .

STEM CELL RESEARCH & THERAPY, 2015, 6

[6] Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression [J].

Balint, K ;

Xiao, M ;

Pinnix, CC ;

Soma, A ;

Veres, I ;

Juhasz, I ;

Brown, EJ ;

Capobianco, AJ ;

Herlyn, M ;

Liu, ZJ .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) :3166-3176

[7] Markers for Characterization of Bone Marrow Multipotential Stromal Cells [J].

Boxall, Sally A. ;

Jones, Elena .

STEM CELLS INTERNATIONAL, 2012, 2012

[8] Notch Pathway Modulation on Bone Marrow-Derived Vascular Precursor Cells Regulates Their Angiogenic and Wound Healing Potential [J].

Caiado, Francisco ;

Real, Carla ;

Carvalho, Tania ;

Dias, Sergio .

PLOS ONE, 2008, 3 (11)

[9] The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP) Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation [J].

Cervelli, V. ;

Garcovich, S. ;

Bielli, A. ;

Cervelli, G. ;

Curcio, B. C. ;

Scioli, M. G. ;

Orlandi, A. ;

Gentile, P. .

BIOMED RESEARCH INTERNATIONAL, 2014, 2014

[10] PRL Platelet Rich Lipotransfert: Our Experience and Current State of Art in the Combined Use of Fat and PRP [J].

Cervelli, V. ;

Bocchini, I. ;

Di Pasquali, C. ;

De Angelis, B. ;

Cervelli, G. ;

Curcio, C. B. ;

Orlandi, A. ;

Scioli, M. G. ;

Tati, E. ;

Delogu, P. ;

Gentile, Pietro .

BIOMED RESEARCH INTERNATIONAL, 2013, 2013

← 1 2 3 4 5 6 7 8 9 10 →