Growth factors (GFs) are critical components in cell therapy, tissue engineering and regenerative medicine. However, growth factors are expensive and are relatively unstable and require constant replenishing when used.
In order to fully exploit the therapeutic potential of GFs, GF delivery vehicles need to meet key design criteria such as providing localized delivery and mimicking the dynamic native GF expression levels and patterns.
TME Therapeutics successfully addresses these key design criteria by using our proprietary technology, TMES (Targeting MicroEnvironment Substrate).
TMES provides customizable, in vivo like microenvironments by presenting ECM mimetics that can activate specific integrin & bind growth factors while also acting as a reservoir for controlled release of growth factors such as EGF, FGF2, PDGF, or TGFβ.
TME Substrates (TMES):
Proprietary Technology for mimicking in vivo microenvironments
Native extracellular matrix (ECM) serves as a scaffold for cell adhesion and growth as well as a reservoir of growth factors (GFs) for release into the extracellular matrix to regulate cell survival, proliferation, and differentiation.
We have developed an ECM mimetic combinatorial library, called the TME Substrate Library. This library is composed of nearly 300 biomimetics of fibronectin, vitronectin, laminin, and collagen that create in vivo like microenvironments. The TME Substrate provides two peptide motifs that simultaneously bind integrin and growth factors, as shown below.
Our TME Substrates, with ECM derived GF binding peptides, can stabilize a broad spectrum of GFs such as FGF2, TGFβ, PDGF, NGF, or VEGF by binding growth factors in a way native ECM does. These growth factors are very important in stem cell expansion as well as tissue engineering. For stem cell expansion, FGF2 and TGFβ are essential components. FGF2, TGFβ, PDGF, and VEGF are key angiogenic growth factors that play a key role in regenerative medicine.
How TMES Substrates work
The ECM-derived integrin binding peptide in the TMES Substrates can facilitate integrin-mediated cell attachment. Cellular GFs are also immobilized and stabilized on the TMES Substrate due to the presence of the GF binding peptide motif.
Cells bound to the TMES Substrate interact directly with adjacent growth factors for cell growth and proliferation.
TMES advantages over exiting technologies
- Reduces costly GF usage by increasing local GF bioavailability to cells
- Increases long-term stability of GF under cell culture conditions by protecting them from enzymatic attack and internalization post-receptor binding
- Immobilization may allow spatial and/or time-controlled presentation to target cells
Benefit: Reduces the manufacturing cost of scaled-up stem cell production
Proof of Concept:
TMES Substrate’s Effect on Mesenchymal Stem Cell Expansion
- Immobilized growth factor surfaces displayed sustained activity over 4 days of culture and retained their functionality in human umbilical cord derived mesenchymal stem cell expansion
- Cells exposed to the immobilized growth factors demonstrated prolonged growth responses relative to soluble growth factors
Proof of Concept:
TMES offers long-term, durable functionality of growth factors
- TMES Substrates have a higher affinity for growth factors compared to heparin; indicating TMES Substrate bound growth factor retains the functionality longer than that of heparin-bound
- Cells exposed to the immobilized growth factors demonstrated a prolonged growth response relative to growth factors in soluble form
TMES Coated Surfaces
Our initially focus is on products related to stem cell expansion under fully defined conditions.
Our TMES coated surfaces support the attachment and expansion of various stem cells including mesenchymal stem cells, satellite stem cells (muscle stem cell), and neural stem cells.
Stem Cell Expansion
- The coated surface facilitates cell attachment mediated by integrin αv including αvβ3 and αvβ5
- GF binding peptides effectively immobilize FGF2, TGFβ and PDGF (with at least 7 days functionality)
TMES Coated Particles
How TMES Particles Work
- TMES particles are nanoparticles ranging in size from 500 nm to 800 nm
- TMES particles are formed by conjugating TMES substrates with negatively charged hyaluronic acid.
- Both peptide motifs (integrin & growth factor binding motif) are attached to the nanoparticle, as seen in the Figure (right)
- TMES Particles can be used as an additive to enhance the performance of your growth factors such as FGF2 and TGFβ
Highlighted Benefits of TMES Particles
- TMES nanoparticles are ECM mimetic substrates with long-term stability under culture conditions for two weeks
- Growth factor bound to TMES particles show longer shelf life compared to native growth factors
- Increased shelf life leads to longer lasting activity of your cells
- Combined with ECM derived peptide (to activate integrin αv), TMES particles can induce synergistic effects on cell growth and proliferation at lower costs compared to GFs in soluble form
TMES Multi-Well Coated Plates For Cell Arrays
Screening to identify optimal ECMs for muscle stem cell (MuSC) expansion
- The TMES MuSC Array design is based on the major ECM components in the MuSC niche (collagen, laminin and fibronectin)
- The TMES Array allows you to quickly and efficiently identify specific ECM motifs that support your stem cell expansion
Customized TMES Products for Cultured Meat
Customized TME Substrates for Your Stem Cell Expansion
- TME has the in-house expertise to optimize your stem cell expansion project.
- Our proprietary TME Substrate technology provides for efficient, cost-effective bioprocessesing.
- Recent application: Clients used our customized product services to successfully optimize muscle stem cell expansion for their cultured meat bioprocess.
Integrins and growth factor receptors are known to regulate the same signaling pathways; and together they regulate cell differentiation, proliferation, and survival. The balance of the various activating and inhibiting signals is considered in determining cell fate.
TME Therapeutics Co., Ltd.
# 208, Insta 2 building, Incheon Startup Park,
204 Convensia-daero, Yeonsu-gu, Incheon, Rep. of KOREA
인천 스타트업파크 내 인스타Ⅱ동 208호
인천시 연수구 컨벤시아대로 204, 대한민국