Matrigel uses in cell biology and for the identification of thymosin b4, a mediator of tissue regeneration

다국어 초록 (Multilingual Abstract)

The thin extracellular matrix that is found basally in epithelial and endothelial cells and around smooth muscle, peripheral nerves, and fat cells is known as the basement membrane. A murine tumor matrix extract, termed Matrigel, has provided an abundant source of basement membrane proteins (laminin, collagen IV, heparan sulfate, etc.). Matrigel gels at room temperature into a structure similar to the authentic matrix. Embryonic tissue explants, stem cells, and various cell types differentiate when cultured on Matrigel. Matrigel has been used in various in vitro assays for angiogenesis, cell invasion, spheroid formation, organoid formation from a single cell, etc. In vivo Matrigel improves/promotes tumor xenograft growth and is used to measure angiogenesis, improve heart and spinal cord repair, increase tissue transplant take, etc.
Endothelial cells plated on top of Matrigel form capillarylike tubules. The gene for thymosin beta 4 was induced at 4 h after plating endothelial cells on Matrigel, and when the thymosin beta 4 protein was added exogenously to the culture, tubule formation was accelerated. Thymosin beta 4, a small 43 kDa protein present in all body fluids and cells, has multiple biological activities, including reducing inflammation, apoptosis, and cytotoxicity while increasing cell migration, stem cell recruitment and differentiation, and tissue repair. Thymosin beta 4 was subsequently found to promote angiogenesis in vivo and to improve dermal and ocular healing in experimental injury models. It has regenerative activity in animal models of traumatic brain injury, stroke, multiple sclerosis, heart attack, peripheral neuropathy, liver and kidney fibrosis, and hair growth.
Clinical trials have demonstrated its efficacy for both stasis and pressure ulcers and for both dry eye and a rare ocular disease. This mini review will discuss the development of Matrigel and the discovery of thymosin beta 4 as a regenerative protein that is upregulated when endothelial cells are plated on Matrigel.

참고문헌 (Reference)

• 1 Dunn SP, "Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta 4" 128 : 636-638, 2010
• 2 Barkan D, "Transition from tumor dormancy to metastatic growth is dependent on the extracellular matrix and cytoskeletal dynamics" 68 : 6241-6250, 2008
• 3 Sosne G, "Thymosin beta 4 significantly improves the signs and symptoms of severe dry eye in a phase 2randomized trial" 34 : 491-496, 2015
• 4 Kleinman HK, "Thymosin beta 4 promotes dermal healing" 102 : 251-275, 2016
• 5 Sosne G, "Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo" 72 : 605-608, 2001
• 6 Sosne G, "Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury" 74 : 293-299, 2002
• 7 Hinkel R, "Thymosin beta 4 is an essential paracrine factor of embryonic endothelial progenitor cell-mediated cardioprotection" 117 : 2232-2240, 2008
• 8 Kim S, "Thymosin beta 4 has a major role in dermal burn wound healing that involves actin cytoskeletal remodeling" 11 : 1262-1273, 2017
• 9 Ehrlich HP, "Thymosin beta 4 enhance repair by organizing connective tissue and preventing the appearance of myofibroblasts" 1194 : 118-124, 2010
• 10 Goldstein AL, "Thymosin b4:actin-sequestering protein moonlights to repair injured tissues" 11 : 421-429, 2005
• 11 Themistoceous GS, "Threedimensional type I collagen cell culture systems for the study of bone pathophysiology" 18 : 687-696, 2004
• 12 Albini A, "The ‘chemoinvasion’ assay, 25 years and still going strong: the use of reconstituted basement membranes to study cell invasion and angiogenesis" 22 : 677-689, 2010
• 13 Treadwell T, "The regenerative peptide thymosin beta 4accelerates the rate of healing of pressure and venous stasis ulcers: analysis of two phase 2 randomized clinical trials" 1270 : 37-44, 2012
• 14 Arnaoutova I, "The endothelial cell tube formation assay on basement membrane turns 20" 12 : 267-274, 2009
• 15 Carey DJ, "Schwann cell myelination:induction by exogenous basement membrane-like extracellular matrix" 102 : 2254-2263, 1986
• 16 Hoffman MO, "Role of laminin-1 and TGF-beta 3 in acinar differentiation of a human submandibular gland cell line (HSG)" 109 : 2013-2021, 1996
• 17 Kubota Y, "Role of laminin and basement membrane in the differentiation of human endothelial cells into capillary-like structures" 107 : 1589-1597, 1988
• 18 Kleinman HK, "Role of collagenous matrices in the adhesion and growth of cell" 88 : 473-485, 1981
• 19 Garcez PP, "Rehen SK(2016)Zika virus impairs growth in human neurospheres and brain organoids" 352 (352): 816-818, 2016
• 20 Hauser BR, "Regulatory mechanisms driving salivary gland organogenesis" 115 : 111-130, 2015
• 21 Bissell MJ, "Regulation of functional cytodifferentiation and histogenesis in mammary epithelial cells: role of the extracellular matrix" 80 : 61-70, 1999
• 22 Chae Eun Kim, "RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model" Springer Nature 8 (8): 2018
• 23 Lugassy C, "Pilot study on ‘‘pericytic mimicry’’ and potential embryonic/stem cell properties of angiotropic melanoma cells interacting with the abluminal vascular surface" 6 : 19-29, 2013
• 24 Cristobal A, "Personalized proteome profiles of healthy and tumor colon organoids reveal both individual diversity and basic features of colorectal cancer" 18 : 263-274, 2017
• 25 Benton G, "Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with tumor cells" 128 : 1751-1757, 2012
• 26 Zadran S, "Monitoring extra-vascular migratory metastasis (EVMM) of migrating cancer cells using an in vitro co-culture system" 2013 : 2867-, 2013
• 27 Benton G, "Matrigel: from discovery and ECM mimicry to assays and models for cancer research" 79-80 : 3-18, 2016
• 28 Kleinman HK, "Matrigel: basement membrane matrix with biological activity" 15 : 378-386, 2005
• 29 Grant DS, "Matrigel induces thymosin beta4 gene in differentiating endothelial cells" 108 : 3685-3694, 1995
• 30 Fridman R, "Increased initiation and growth of tumor cell lines, cancer stem cells, and biopsy material in mice using basement membrane proteins (Cultrex/Matrigel) coinjection" 17 : 1138-1144, 2012
• 31 Benton G, "In vitro microtumors provide a physiological predictive tool for breast cancer therapeutic screening" 10 (10): e0123312-, 2015
• 32 Arnaoutova I, "In vitro angiogenesis:endothelial cell tube formation on a gelled basement membrane extract" 5 : 628-635, 2010
• 33 Lin Y, "Effect of thymosin beta 4 on the survival of random skin flaps in rats" 31 : 464-470, 2015
• 34 Pasquier J, "Coculturing with endothelial cells promotes in vitro maturation and electrical coupling of human embryonic stem cell-derive cardiomyocytes" 36 : 684-693, 2017
• 35 Kleinman HK, "Basement membrane complexes with biological activity" 25 : 312-318, 1986
• 36 Fridman R, "Basement membrane (matrigel) enhances both the incidence and growth of subcutaneously injected human and murine cells" 83 : 769-774, 1991
• 37 Arnaoutova I, "Basement membrane (BME) has multiple uses with stem cells" 8 : 163-169, 2012
• 38 Gho YS, "Angiogenic activity of human soluble intercellular adhesion molecule-1" 59 : 5128-5132, 1999
• 39 Benton G, "Advancing science and technology via 3D culture on basement membrane matrix" 221 : 18-25, 2009
• 40 Allan L Goldstein, "Advances in the basic and clinical applications of thymosin β 4" Informa Healthcare 15 (15): 139-145, 2015
• 41 Albini A, "A rapid in vitro assay for quantitating the invasive potential of tumor cells" 47 : 3239-3245, 1987