Exosomes for repair, regeneration and rejuvenation

ABSTRACT

Introduction: Application of regenerative medicine strategies for repair of organs/tissue impacted by chronic disease is an active subject for product development. Such methodologies emphasize the role of stem cells as the active biological ingredient. However, recent developments in elucidating mechanisms of action of these therapies have focused on the role of paracrine, ‘action-at-a-distance’ modus operandi in mediating the ability to catalyze regenerative outcomes without significant site-specific engraftment. A salient component of this secreted regenerative milieu are exosomes: 40–100 nm intraluminal vesicles that mediate transfer of proteins and nucleic acids across cellular boundaries.

Areas covered: Here, we synthesize recent studies from PubMed and Google Scholar highlighting how cell-based therapeutics and cosmeceutics are transitioning towards the secretome generally and exosomes specifically as a principal modulator of regenerative outcomes.

Expert opinion: Exosomes contribute to organ development and mediate regenerative outcomes in injury and disease that recapitulate observed bioactivity of stem cell populations. Encapsulation of the active biological ingredients of regeneration within non-living exosome carriers may offer process, manufacturing and regulatory advantages over stem cell-based therapies.

KEYWORDS:

• Exosome
• micro-vesicle
• extra-cellular vesicle
• cell therapy
• tissue engineering
• regenerative medicine
• stem cell
• progenitor cell
• organogenesis
• morphogen
• manufacturing
• quality control
• regulatory

Article highlights

• Exosomes participate in key mechanistic pathways in development, organogenesis, wound healing and regeneration in adults by mediating intercell communication of key developmental morphogens and other signaling elements.

• Exosomes can reprogram target cells toward acquisition of characteristics associated with the donor cell, including differentiated or stem cell-like phenotypes.

• Regenerative bioactivity associated with stem and progenitor cell populations can be recapitulated by conditioned media isolated from the culture, maintenance and expansion of those populations. At least part of this bioactivity is specific to microvesicles, including exosomes.

• Purified exosomes have been demonstrated to have clinically relevant therapeutic bioactivity across multiple in vitro and in vivo models.

• Compared with cells, exosomes are more stable and storable, have no risk of aneuploidy, a lower possibility of immune rejection following in vivo allogeneic administration, and may provide an alternative therapy for various diseases.

• Secretomic products including exosomes are being developed as cosmeceuticals.

• Methodologies for the industrial scale manufacture of exosome-based therapeutics and the associated regulatory and quality control infrastructure remain generally undefined.

• Tunable exosomes, synthetic exosomes and exosome mimetics, as well as exosomes engineered to overexpress or knockdown signaling pathways associated with disease pathology, represent the next generation of exosome-based product candidates to be developed.

This box summarizes key points in the article.

Acknowledgment

The authors are grateful to Randal McKenzie (McKenzie Illustrations, [email protected]) for the graphics in Figure 1.

Declaration of interest

This work has been funded by ZenBio, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.