LiverCell FAQ

Can the Liver regenerate?

The capability of the liver to fully regenerate after injury is a unique phenomenon essential for the maintenance of its important functions in the control of metabolism and xenobiotic detoxification.

Liver regeneration is the process by which the liver is able to replace lost liver tissue from growth from the remaining tissue. The liver is the only visceral organ that possesses the capacity to regenerate.[1][2] The liver can regenerate after either surgical removal or after chemical injury.[3] It is known that as little as 25% of the original liver mass can regenerate back to its full size.[2][4] The process of regeneration in mammals is mainly compensatory growth because only the mass of the liver is replaced, not the shape.[5]

What proteins are important to liver regeneration?
Interleukin 6, IGF1, TNFa, VEGF, HGF, EGF, Klotho, Tropoelastin, eNOS Sonic Hedgehog, CXCL5, Neurogenin 3, Follistatin, FGF, WnT proteins, TGFb, Jagged, Delta and Notch proteins, Activins, BMPs, SDF1, PDGF, HIF1a.

TNFα and IL-6 are thought to play major roles in initiating the process of liver regeneration.

Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of liver regeneration includes three phases: priming stage, proliferative phase, and termination phase. The initial step aims to induce hepatocytes to be sensitive to growth factors with the aid of some cytokines, including TNF-α and IL-6. The proliferation phase promotes hepatocytes to re-enter G1 with the stimulation of growth factors. While during the termination stage, hepatocytes will discontinue to proliferate to maintain normal liver mass and function. Except for cytokine- and growth factor-mediated pathways involved in regulating liver regeneration, new substances and technologies may emerge through further research to influence the regenerative process.

What is LiverCell EndoBioelectric therapy?
Using a direct conductive lead or nerve pathways a bioelectric stimulator delivers to the liver a series of bioelectric signaling sequences that home reparative stem cells to the liver, grow new blood supply, release regenerative proteins and differentiated stem cells into living functioning new liver tissue.
What is LiverCell EndoBioelectric + Biologics therapy?
In addition to bioelectric stimulation therapy a re-fillable micro infusion pump is used (often with two chambers) to deliver slow infusions directly or nearly directly into the liver of the LC-15 fifteen component liver regeneration composition comprised of adipose tissue derived cells and stromal fraction, PRF, regenerative fluid derived from amniotic sourcing, micro RNA gel, selected growth factors, growth hormone, selected exosomes, oxygenated nanoparticles, nutrient hydrogel, selected alkaloids and liver matrix. The biologics therapy may be supplemented with patient specific liver cells harvested, cultured and multiple in a laboratory and re-injected into the patient via a re-fillable slow infusion micro pump.
What is LiverCell Non-Invasive therapy?
Non-Invasive delivery of bioelectric signaling sequences and in severe cases IV infusion of the LC-15 cocktail composition for liver regeneration.
What does controlled expression of SDF1 and PDGF do for liver regeneration?
Home/recruit stem cells from a patient’s own bone marrow, fat tissue and circulating blood to their liver.
What does controlled expression of Klotho do for liver regeneration?
Klotho is a known anti-aging protein with powerful regeneration support capabilities is required for FGF19 binding to FGFR4, intracellular signaling, and downstream modulation of gene expression in regenerating livers.
What does controlled expression of Sonic Hedgehog do for liver regeneration?
Hedgehog signaling is critical for normal liver regeneration.
What does controlled expression of IGF1 do for liver regeneration?
IGF-I is expressed in virtually every tissue of the body, but with much higher expression in the liver than in any other tissue. GH is a member of the cytokine superfamily of polypeptide regulators (13). The growth-promoting effects of GH can be direct in selected target tissues, such as liver, or indirectly, via its endocrine mediator IGF-I. GH is the primary regulator of IGF-I synthesis and secretion in hepatocytes; in turn, IGF-I regulates GH secretion IGF1 and GH play a major role in the process of liver regeneration. Recent studies have clarified the essential roles of GH and IGF-I in the liver. GH profoundly reduces visceral fat, which plays an important role in the development of NAFLD. Furthermore, GH directly reduces lipogenesis in the hepatocytes. IGF-I induces cellular senescence and inactivates hepatic stellate cells, therefore ameliorating fibrosis. IGF-I treatment has been shown to improve animal models of NASH and cirrhosis, suggesting potential clinical applications of IGF-I in these conditions.
What does controlled expression of HGF do for liver regeneration?

Hepatocyte growth factor gene therapy accelerates regeneration in …


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773642/

by F Xue – ‎2003 – ‎Cited by 104 – ‎Related articles …

Hepatocyte growth factor stimulates liver regeneration and elevates blood protein level in normal and partially hepatectomized rats.

Abstract

The effects of recombinant human hepatocyte growth factor (HGF) on liver growth and function of normal and partially hepatectomized rats have been examined. HGF was continuously administered into the jugular vein because it was rapidly eliminated from the plasma (t1/2 alpha; approximately 4.5 min) and degraded. In normal rats, the labeling index of hepatocytes was increased about 6 times by the administration of HGF. HGF also decreased the prothrombin time and increased the hepaplastin and serum albumin content. In 70%-hepatectomized rats, HGF stimulated liver regeneration and increased the level of blood proteins such as hepaplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell number but also the direct effect of HGF on the protein production in hepatocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF further accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.
What does controlled expression of EGF receptor do or liver regeneration?
Studies demonstrate that EGFR is a critical regulator of hepatocyte proliferation in the initial phases of liver regeneration.
 

Epidermal growth factor receptor restoration rescues the fatty liver …


https://www.physiology.org/doi/full/10.1152/ajpendo.00032.2017?view=long…
Where can I read more?

Understanding Liver Regeneration – The American Journal of Pathology


https://ajp.amjpathol.org/article/S0002-9440(17)31026-X/fulltext
Apr 16, 2018 – When Sonic hedgehog (Shh) binds to Patched (Ptch) receptor, … Hedgehog signaling is critical for normal liver regeneration after partial …
 

Liver Regeneration: Analysis of the Main Relevant Signaling Molecules


https://www.hindawi.com/journals/mi/2017/4256352/

by Y Tao – ‎2017 – ‎Cited by 20 – ‎Related articles

Aug 10, 2017 – Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of …

 

Mesenchymal stem cells accelerate liver regeneration in acute liver …


www.bmrat.org/index.php/BMRAT/article/view/498/996

by A Putra – ‎2018 – ‎Related articles

Mesenchymal stem cells (MSCs) have a critical role in the regeneration of liver injury through regulating platelet-derived growth factor (PDGF) and vascular …

 

Clinical implications of advances in liver regeneration


https://www.e-cmh.org/m/makeCookie.php?url=/m/journal/view.php?number…

by YJ Kwon – ‎2015 – ‎Cited by 39 – ‎Related articles

Mar 25, 2015 – When the liver volume returns to its own size, activin A, apoptosis and other factors may terminate the regeneration process.14 Table 2 …

MicroRNAs in Liver Regeneration – FullText – Cellular Physiology and …


https://www.karger.com/Article/FullText/430381

by X Chen – ‎2015 – ‎Cited by 19 – ‎Related articles

Sep 8, 2015 – Liver maintains a unique tremendous regeneration capacity in response to … between miR-34a and activin-A in termination regenerating livers

 

Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies …


https://www.hindawi.com/journals/bmri/2017/8910821/

by IV Kholodenko – ‎2017 – ‎Cited by 22 – ‎Related articles

Dec 27, 2016 – Liver regeneration is activated spontaneously after injury and can …. Normal liver tissue contains relatively small amount of extracellular matrix …

 

The alterations in the extracellular matrix composition guide the repair …


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893701/

by M Klaas – ‎2016 – ‎Cited by 35 – ‎Related articles

Jun 6, 2016 – While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is …

 

Nanoparticles for the treatment of liver fibrosis – NCBI


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614791/

by SP Surendran – ‎2017 – ‎Cited by 7 – ‎Related articles

Keywords: liver fibrosis, inorganic nanoparticles, liposomes, micelles … nodules of regeneratinghepatocytes defines cirrhosis, ie, the so-called advanced liver fibrosis. … in the production of acet-aldehyde and reactive oxygen species (ROS).

 

Hydrogel nudges stem cells to grow into liver cells – Futurity


https://www.futurity.org/hydrogel-stem-cells-liver-cells-1884392/

Oct 8, 2018 – The new nanomaterial-based hydrogel, which gets certain stem … metabolism, immunity, and storage of nutrients within the body. … The research appears in the Journal of Tissue Engineering and Regenerative Medicine.

Development of hydrogels for regenerative engineering – NCBI


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503693/

by X Guan – ‎2017 – ‎Cited by 41 – ‎Related articles

May 1, 2018 – In addition, current hydrogel-based regenerative engineering strategies …. lung, liver, kidney, cartilage, bone, retina, trachea, and dermis using various …. scale to efficiently supply fluid and nutrients to the peripheral tissues.

Injectable hydrogels delivering therapeutic agents for disease … – NCBI


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158836/

by JH Lee – ‎2018 – ‎Cited by 1 – ‎Related articles

Sep 26, 2018 – In this article, recent studies of injectable hydrogel systems applicable … reaction, Disease and cancer therapy, Tissue repair and regeneration … permeability to oxygen and nutrient, physical properties similar to the ….. nerve, cornea, skin, bone, several organs including liver and kidney, dental, and so on.

3-D culturing hepatocytes on a liver-on-a-chip device – Phys.org


https://phys.org › Chemistry › Analytical Chemistry

Jan 17, 2019 – Liver-on-a-chip cell culture devices are attractive biomimetic models in drug … across the hydrogel surface for steady nutrient media exchange, to and from the …. in drug toxicology, drug discovery and regenerative medicine.

[PDF]

Fibrin Hydrogels for Endothelialized Liver Tissue Engineering … – MDPI


https://www.mdpi.com/2073-4360/10/10/1048/pdf

by X Wang – ‎2018 – ‎Cited by 2 – ‎Related articles

Sep 20, 2018 – Fibrin Hydrogels for Endothelialized Liver Tissue. Engineering with a … organ implantation, which provides nutrients and removes metabolites for multi-cellular tissues. … engineering and regenerative medicine. Numerous …

LIVER DISEASE

PREVALENCE & MARKET SIZE

  • 4.5 million Americans have diagnosed liver disease
  • 30 million Americans are suffering from some form of fatty liver disease 5/6th’s undiagnosed.
  • Nearly 2% of all Americans have liver disease
  • 4.5 to 9% of people worldwide have liver disease
  • Liver disease is responsible for more than 2 million deaths worldwide annually.
  • Liver cirrhosis is the 11th leading cause of death worldwide.
  • The Non-alcoholic Steatohepatitis (NASH) market alone is expected to reach $18.3 billion by 2026.
  • Experts forecast the liver disease treatment market to be soon reaching $19.5 billion.