LiverCell

bioLiverCell is a startup within the Leonhardt Ventures Cal-X Stars Business Accelerator and Leonhardt’s Launchpads Utah focused on liver regeneration.

The company utilizes bioelectric stimulation to control release of specific proteins on demand for specific regenerative purposes in sequence:

1. SDF-1 (stem cell homing factor – recruits a persons own stem cells to stimulated tissues).

2. VEGF (for new blood vessel growth).

3  IGF-1 (for DNA repair at the nucleus level). 

4. Follistatin (for muscle and tissue regeneration).

5. RANKL (for demineralization and tissue loosening when needed).

6. Hepatocyte Growth Factor  (tissue regeneration)

7. eNOS (for dilating blood vessels for increasing flow).

8.  Tropoelastin (increases elasticity of any tissues such as skin, arteries, aorta, heart and promotes healing of wounds). 

9. Activin

In extreme cases we combine our regeneration microstimulator with an implantable, programmable, re-fillable stem cell/growth factor micro pump.

In cases of liver cancer we have special signals to stop tumor cell division and blood supply followed by the above regeneration protocol. 

RELATED SCIENTIFIC SUPPORTING ARTICLES:

Regulation of liver regeneration by growth factors and …

www.ncbi.nlm.nih.gov/…

National Center for Biotechnology Information

by F Böhm – ‎2010 – ‎Cited by 74 – ‎Related articles

Figure 1. The different cell types of the liver and liver regeneration after ….. factor showed delayed liver regeneration due to insulin/IGF1 resistance that was …

http://www.pubfacts.com/detail/26939868/VEGF-sdf1-RECRUITMENT-OF-CXCR7-BONE-MARROW-PROGENITORS-OF-LIVER-SINUSOIDAL-ENDOTHELIAL-CELLS-PROMOTE

VEGF-sdf1 RECRUITMENT OF CXCR7+ BONE MARROW PROGENITORS OF LIVER SINUSOIDAL ENDOTHELIAL CELLS PROMOTES RAT LIVER REGENERATION.

Am. J. Physiol. Gastrointest. Liver Physiol.

Am J Physiol Gastrointest Liver Physiol 2016 Mar 3:ajpgi.00056.2016. Epub 2016 Mar 3.

Laurie D DeLeveXiangdong WangLei Wang

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In liver injury, recruitment of bone marrow progenitors of liver sinusoidal endothelial cells (now named sprocs) is necessary for normal liver regeneration. Hepatic VEGF is a central regulator of the recruitment process. Here we examine whether stromal cell derived factor-1 (sdf-1 or CXCL-12) acts downstream from VEGF to mediate recruitment of bone marrow sprocs, what the sdf-1 receptor type (CXCR4 or CXCR7) is on sprocs, and whether sdf-1 signaling is required for normal liver regeneration.

Studies were performed in the rat partial hepatectomy model. Tracking studies of bone marrow sprocs were performed in wild type Lewis rats that had undergone bone marrow transplantation from transgenic EGFP+ Lewis rats. Knockdown studies were performed using anti-sense oligonucleotides.

Expression of sdf-1 doubles in liver and in LSECs after partial hepatectomy. The upregulation of sdf-1 expression increases proliferation of sprocs in the bone marrow, mobilization of CXCR7+ bone marrow sprocs to the circulation, and engraftment of CXCR7+ bone marrow sprocs in the liver, and promotes liver regeneration. Knockdown of hepatic VEGF with anti-sense oligonucleotides decreases hepatic sdf-1 expression and plasma sdf-1 levels. When the effect of VEGF knockdown on sdf-1 is offset by infusion of sdf-1, VEGF knockdown-induced impairment of BM sproc recruitment after partial hepatectomy is completely attenuated and liver regeneration is normalized.

These data demonstrate that the VEGF-sdf-1 pathway regulates recruitment of CXCR7+ bone marrow sprocs to the hepatic sinusoid after partial hepatectomy and is required for normal liver regeneration.

Affiliation

University of Southern California Keck School of Medicine.

[PDF]

Signals and Cells Involved in Regulating Liver Regeneration

www.mdpi.com/2073-4409/1/4/1261/pdf

MDPI

by LI Kang – ‎2012 – ‎Cited by 30 – ‎Related articles

Dec 13, 2012 – Keywords: liver regeneration; hepatocyte; hepatocyte growth factor; epidermal growth factor … IGF1), as well as other functions. The ability of ..

Hepatocyte proliferation during liver regeneration is …

www.fasebj.org/content/20/6/773.full

The FASEB Journal

by C Desbois-Mouthon – ‎2006 – ‎Cited by 82 – ‎Related articles

Feb 16, 2006 – To test whether IGF-1R regulates liver regeneration, we performed partial hepatectomy in liver-specific IGF type 1 receptor knockout …

HGF and SDF-1-mediated mobilization of CD133+ BMSC …

www.ncbi.nlm.nih.gov/…

National Center for Biotechnology Information

by N Lehwald – ‎2014 – ‎Cited by 12 – ‎Related articles

May 23, 2013 – 1Liver Int. 2014 Jan;34(1):89-101. doi: 10.1111/liv.12195. … of CD133+ BMSC for hepatic regeneration following extensive liver resection.

SDF-1/CXCR4 Axis Promotes MSCs to Repair Liver Injury …

www.hindawi.com/journals/sci/aa/960387/

by NB Hao – ‎Related articles

Mar 6, 2015 – SDF1/CXCR4 Axis Promotes MSCs to RepairLiver Injury Partially … been a popular topic in regenerativemedicine and have generated a …

involvement of sdf-1 in stem cell-aided liver regeneration

ufdcimages.uflib.ufl.edu/UF/E0/01/36/86/00001/zheng_d.pdf

INVOLVEMENT OF SDF1 IN STEM CELL-AIDED LIVER REGENERATION. By. DONGHANG ZHENG. A DISSERTATION PRESENTED TO THE GRADUATE …

A single intraportal administration of follistatin … – NCBI

www.ncbi.nlm.nih.gov/…

National Center for Biotechnology Information

by K Kogure – ‎1995 – ‎Cited by 98 – ‎Related articles

A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats. Kogure K(1), Omata W, Kanzaki M, Zhang YQ, …

Activin or follistatin: which is more beneficial to support liver …

www.ncbi.nlm.nih.gov/…/1… National Center for Biotechnology Information

by D Endo – ‎2006 – ‎Cited by 37 – ‎Related articles

Endocr J. 2006 Feb;53(1):73-8. Activin or follistatin: which is more beneficial to support liver regeneration after massive hepatectomy? Endo D(1), Maku-Uchi M, …

Reversibility of liver fibrosis | Fibrogenesis & Tissue Repair …

fibrogenesis.biomedcentral.com/articles/10.1186/1755-1536-5-S1-S26

by A Pellicoro – ‎2012 – ‎Cited by 52 – ‎Related articles

Jun 6, 2012 – We have shown that elastin turnover in liver injury and fibrosis is regulated … step in the interlinked processes of tissue injury and regeneration.

VEGF is Important for Early Liver Regeneration After Partial …

www.sciencedirect.com/science/…/S0022480406003933

ScienceDirect

by M Bockhorn – ‎2007 – ‎Cited by 71 – ‎Related articles

VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given …

Roles of vascular endothelial growth factor and endothelial …

link.springer.com/…/10.1007%2Fs00595-… Springer Science+Business Media

by D Yoshida – ‎2011 – ‎Cited by 13 – ‎Related articles

Liver regeneration and SEC proliferation were evaluated. The protein expression of VEGF and eNOS was examined by a Western blot analysis. The rats were …

Signals and Cells Involved in Regulating Liver Regeneration

www.mdpi.com/2073-4409/1/4/1261/pdf

Bone marrow stem cells and liver disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1942133/

Summary:

  1. SDF-1/CXCR4 signaling central to BMSC homing to liver
  2. BMSCs support liver repair through the delivery of growth factors that promote liver regeneration, fibrosis resolution or new blood vessel formation
    • Of specific interest, BMSCs upregulate HGF which may play a role in diminishing fibrosis

Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis

http://www.ncbi.nlm.nih.gov/pubmed/15793283/