Breakthrough in Patient-Derived Stem Cells for Therapeutic Regenerative Medicine

Minerva Biotechnologies published, “The Wnt pathway induces a naïve-like subpopulation in primed stem cells, while NME7_AB leads to a homogeneous naïve-like population,” in the journal PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0325997

These studies shed light on the scientific controversy of whether activation of the Wnt/β-catenin pathway induces human stem cell pluripotency or differentiation. The literature is replete with contradictory conclusions, based on what appear to be sound scientific studies. Others reported that low levels of β-catenin skew differentiation down neuroectoderm, whereas high levels favor differentiation down mesendoderm. Recently two research groups independently found that “boosting” β-catenin just prior to differentiation improved differentiation of both neuroectoderm and mesendoderm.

Unexpectedly, our studies found that, in the absence of other growth factors, activation of the Wnt/β-catenin pathway induced two segregated populations: islands of naïve OCT4+ XaXa cells (both X chromosomes active) in a sea of differentiating OCT4- XaXi cells (one X chromosome inactivated). Like others, we found that activating the β-catenin pathway before or at the initiation of differentiation greatly improved the differentiation of primed state stem cells but had no effect on NME7 _AB naïve state stem cells. The differentiation of homogeneous populations of NME7 _AB induced naïve state stem cells was superior to that of primed state stem cells, even if the β-catenin pathway was activated before differentiation. For example, induced pluripotent stem cells (iPSC) generated in, then expanded in GMP compliant minimal media containing recombinant NME7_AB as the only growth factor, differentiated with high efficiency into mesenchymal stem cells (MSCs). Unlike other attempts, Minerva’s iPSC-derived MSCs resisted senescing and each clone could differentiate into essentially pure populations of chondrocytes, osteoblasts or adipocytes that could be useful for repair or replacement of cartilage, bone or fat.

“These data represent a major breakthrough for the large-scale, GMP compliant manufacture of patient-derived MSCs for therapeutic uses,” said Dr. Cynthia Bamdad, CEO of Minerva Biotechnologies, “and will replace the practice of using MSCs harvested from bone marrow of unknown, often untested donors.”

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