#

Regenerative Medicine

###

Enabling the True Potential of Regenerative Medicine

Patient-derived induced pluripotent stem cells (iPSCs) offer exciting potential for disease modeling, regenerative medicine, and therapeutic development. In order to fully realize the potential of iPSCs, it is critical to develop culture and differentiation methodologies that result in the most biologically relevant terminal cell types.

Minerva Biotechnologies is the first company to generate human naïve state induced pluripotent stem cells (iPS cells) using a single, naturally occurring human stem cell growth factor, NME7AB. Naïve stem cells have several advantages over current stem cells, called ‘primed’ state cells. Scientists believe that because these earlier stem cells have a “clean slate”, they are more easily directed to develop into functional mature cells. Using AlphaSTEM™ Culture System, differentiation efficiency is increased and the resulting cells have enhanced functionality. 

Currently, many stem cell culture scientists work with cells that require LIF and/or bFGF and numerous small molecules, such as demethylases and MAP kinase inhibitors, to keep their stem cells in a naïve-like state.  While this achieves similar cell culture conditions to naïve stem cells, there are significant differences in gene expression profiles of naïve-state markers, a decrease in differentiation potential, and unstable karyotypes.  

Neurobiology 

Minerva’s AlphaSTEM™ Culture System increases directed differentiation to neural cells by 150X over FGF media. When AlphaSTEM®  Differentiation Inducer is used, the increase is 250X. 

Cardiovascular

The yield, intensity of contraction and synchronization of beating is greater in cardiomyocytes differentiated from AlphaSTEM®  cultured cells than FGF primed state cells

AlphaSTEM®  Cultured Stem Cells

  • Strong contraction
  • Coordinated beating
  • High yields: 80-100% eliminating need for suicide genes or lactate purification
 

FGF Cultured Stem Cells

  • Weak contraction
  • Uncoordinated beating 
  • Low yields: 15-40% - requiring suicide genes or lactate purification

 

 

Sarcomeres are the basic unit of muscle to which myosin and actin attach and cause the contraction in cardiomyocytes. Immunofluorescent imaging of α-actinin shows that cardiomyocytes derived from AlphaSTEM®  naïve stem cells have a more organized sarcomere structure compared to those derived from FGF2 primed cells, which gives rise to more effective contractions. 

 

Publications

  1. A Primitive Growth Factor, NME7AB, Is Sufficient to Induce Stable Naïve State Human Pluripotency; Reprogramming in This Novel Growth Factor Confers Superior Differentiation
  2. MUC1* ligand, NM23-H1, is a novel growth factor that maintains human stem cells in a more naïve state.
  3. MUC1* mediates the growth of human pluripotent stem cells