Secretomix® offers great potential for regenerative medicine and patient care. Through the secretome’s ability to simultaneously act on numerous cell signalling pathways, Micregen aims to provide a novel treatment for multiple conditions associated with ageing.
A stem cell’s ability to self-renew and differentiate offers the potential to regenerate and repair tissues. However, there were four significant challenges.
- The first challenge we faced when considering stem cell treatment was understanding how stem cells function in the injured microenvironment. We identified these mechanisms and are now translating our preclinical findings to human studies (Mellows, Mitchell et al. 2017, Mitchell, Mellows et al. 2019).
- The second challenge was identifying and isolating the key regenerative factors that Secretomix® use to induce repair and regeneration and then optimise production of these factors to create a scalable product.
- The next challenge was avoiding immune rejection. Secretomix® escape immunological rejection partly because they derive from developmentally naïve and immunologically privileged stem cells while bypassing the need for whole-cell transplants. This creates a treatment that most people can use, rather than one only used by the donor. In addition, this means that Secretomix® can be administered immediately at the point of care for multiple recipients with minimal immunological risk.
- Proprietary manufacturing processes and a developed allogeneic cell line enabled Micregen to overcome the final challenge of scaling up the production of Secretomix® to provide a cost-effective therapy that the majority can use and the starting material for a variety of degenerative diseases for years to come.
Micregen’s intellectual property continues to build around its novel platform technology that overcomes these challenges and, if successful in human trials, will offer significant manufacturing and clinical advantages.
Secretomix® offers great potential for regenerative medicine and patient care. Through the secretome’s ability to simultaneously act on numerous cell signaling pathways, Micregen aims to provide novel treatments for multiple complex degenerative conditions of high unmet need.
A stem cell’s ability to self-renew and differentiate offers the potential to regenerate and repair tissues. However, there were four significant technical challenges:
| Benefits of Secretome |
|---|
Understanding how stem cells function in the injured microenvironment – We identified key mechanisms and are now translating our preclinical findings to human studies (Mellows, Mitchell et al. 2017, Mitchell, Mellows et al. 2019). |
Identifying and isolating the key regenerative factors that Secretomix® use to induce repair and regeneration and then optimise production of these factors to create a scalable product. We have characterised our leading Secretomix® formulations and identified over 2,000 components together with key pathways they effect. |
Reducing the risk of immune rejection – Secretomix® are isolated from developmentally naive and immunologically privileged stem cells whilst being a cell-free product |
Scaling up the production of Secretomix® to provide a cost-effective therapy – Proprietary manufacturing processes and a GMP developed allogeneic cell line enables Micregen to create ‘off-the-shelf’ therapeutic candidates and retain stable and reproducible starting material for a variety of degenerative diseases for years to come. |
| Challenge (Traditional Stem Cell Therapies) | Secretomix® Solution |
|---|---|
Limited cell engraftment into target tissue |
Cell-free secretome delivers regenerative factors directly |
Variability & inconsistency in donor cells |
Produced from GMP-certified, defined stem cell banks ensuring reproducibility |
Risk of immune rejection or graft complications |
Cell-free & immunologically privileged, suitable for all patients |
Risk of uncontrolled differentiation/tumour formation |
No whole cells used → safer therapeutic profile |
Difficulty in large-scale production |
Scalable, consistent, off-the-shelf manufacturing process |
Need for ultra-cold storage |
Secretomix® is stable & storable under standard conditions |
Micregen’s intellectual property continues to build around its novel platform technology that aims to overcome these challenges and, if successful in human trials, will offer significant manufacturing and clinical advantages.
MRG1061 is produced from MRG_iA_37, our proprietary immortalised amniotic fluid stem cell line, held in GMP-grade master and working cell banks engineered with Merck. Guiding those cells through controlled conditions determines what they secrete, and therefore what the product does.
- Consistent – an immortalised line supports a more consistent and scalable manufacturing process than more variable primary cell cultures
- Characterised – 566 microRNA species and 1,907 proteins identified by independent characterisation; 21 in-process-control and release assays developed, including a potency assay designed to measure a biologically relevant activity of the product
- Stable – over 4 years of stability data completed; no ultra-cold chain required
- Scalable -designedformanufactureatGMPcontractfacilities and multi-patient batch yield
- Off-the-shelf – allogeneic, administered at the point of care with no donor
As a multimodal biologic, Secretomix® acts simultaneously on several of the mechanisms that drive tissue regeneration. In preclinical studies we have associated it with the ability to modulate inflammation, reduce cellular senescence, activate resident stem and progenitor cells, improve angiogenesis and restore autophagy.
Because it acts on several mechanisms at once, Secretomix® has a rationale in more than one disease. That is what makes it a platform rather than a single drug.
Intellectual property. Micregen owns worldwide rights to the Secretomix® platform outright, including the proprietary MRG_iA_37 cell line, the cell banks and the production process.
The use of Secretomix® is aimed to facilitate tissue repair through the modulation of inflammation, altered intercellular communication, recovery of stem cell exhaustion and improved autophagy, generating a pro-regenerative microenvironment across a wide range of organs and tissue types.
Micregen believes their innovative approach can change how multiple acute and chronic problems are managed.
As a cell-free approach, the use of Secretomix® negates the need to introduce whole stem cells into the patient. Therefore, the risk of potential uncontrolled differentiation or tumour development from the use of whole cells is reduced, making a significant advancement to patient safety (Zhang, Gao et al. 2019, Wu, Wang et al. 2022).
These discoveries will enable Micregen to overcome such barriers to translating stem cell derived technology into many areas of medicine.
In recent years there has been an exponential growth in peer-reviewed, published scientific papers confirming Micregen’s approach. (Gnecchi, Zhang et al. 2008, Ranganath, Levy et al. 2012, Lener, Gimona et al. 2015, Ho, Warr et al. 2017, Phinney and Pittenger 2017).
Micregen is currently undertaking several studies to identify the efficacious effects of Secretomix® to tackle degeneration and the effects of ageing in its many guises.
The principal modes of action of stem cell secretomes are:
- Modulation of inflammation
- Decreased cellular senescence
- Activation of resident stem cell and tissue-specific progenitor cell populations
- Improved angiogenesis – enhanced blood flow
- Anti-apoptotic and chemotactic signalling
- Beneficial remodelling of the extracellular matrix
- Regulation of protein catabolism and anabolism
- Reduced mitochondrial dysfunction
- Protection of cells from oxidative stress.
Micregen aims to utilise its Secretomix® platform technology to target the mechanisms underlying degenerative disease (including the hallmarks of ageing) and promote regeneration as opposed to treating just the symptoms of disease. Thus, increasing health span and prolonging the period of life that can be actively lived.