Variability in Donor MSCs Highlights Risks; Cynata’s iPSC Cells Offer Consistency Advantage

Study Overview and Context

On 5 February 2025, Cynata Therapeutics Limited (ASX: CYP) announced the publication of a significant comparative study in npj Regenerative Medicine, a leading peer-reviewed journal from Nature Portfolio. The study, conducted by researchers at Monash University, evaluated the secretome profiles and functional properties of mesenchymal stem cells (MSCs) derived from Cynata’s proprietary Cymerus™ platform, using induced pluripotent stem cells (iPSCs), against MSCs sourced from conventional donor tissues such as bone marrow, adipose tissue, and umbilical cord.

This research is pivotal because the therapeutic efficacy of MSCs largely depends on their secretome, the complex array of proteins and molecules they release, which mediate regenerative and immunomodulatory effects. Traditional MSC manufacturing relies on donor tissue, which introduces variability and supply constraints. Cynata’s Cymerus™ platform circumvents these issues by generating MSCs from a renewable iPSC source, promising scalability and consistency.

Key Findings: Potency and Consistency

The study revealed substantial differences between MSCs depending on their source. Notably, iPSC-derived MSCs secreted a broader array of unique proteins compared to donor tissue-derived MSCs, suggesting a wider therapeutic potential. This expanded secretome profile may translate into additional biological effects not achievable with conventional MSCs.

In addition, batch-to-batch variability, a critical challenge in cell therapy manufacturing, was markedly lower in iPSC-derived MSCs than in donor tissue-derived cells, particularly those from bone marrow. This consistency is crucial for clinical reliability and regulatory approval.

Regenerative and Immunomodulatory Advantages

Functionally, iPSC-derived MSCs and umbilical cord-derived MSCs exhibited characteristics of “younger” cells, maintaining their regenerative capacity and resistance to senescence under both resting and inflammatory conditions. This resilience is important since MSCs often encounter inflammatory environments post-administration.

In vitro assays demonstrated that iPSC-derived MSCs promoted significantly faster wound closure and exerted stronger immunomodulatory effects than MSCs from bone marrow or adipose tissue. All MSC types stimulated angiogenesis, with some measures suggesting umbilical cord MSCs might have a slight edge, though differences were generally minimal.

Implications for Cynata’s Clinical Pipeline

Dr Kilian Kelly, Cynata’s CEO, emphasized that these findings reinforce the advantages of the Cymerus™ platform in producing potent, functional MSCs at scale. The enhanced immunomodulatory and wound healing properties align closely with Cynata’s clinical programs targeting steroid-resistant acute graft versus host disease (GvHD) and diabetic foot ulcers, both of which have demonstrated promising safety and efficacy in early trials.

Prof Jess Frith from Monash University highlighted the importance of cell source in therapeutic design, suggesting that these insights could guide the development of more effective MSC-based treatments and help identify optimal clinical applications.

Looking Ahead

While the study provides robust preclinical evidence supporting Cynata’s approach, the translation of these findings into clinical success will depend on ongoing and future trials. The company’s Phase 2 and Phase 3 studies will be critical in validating the therapeutic superiority and commercial viability of Cymerus™-derived MSCs.