Theme 5: Tissue Engineering for Regenerative Medicine

Theme Leaders:

Professor Jillian Cornish, University of Auckland
Associate Professor Tim Woodfield, University of Otago

Find others working in this area here.

The following series of articles is written by Reg Harris1 in November 2015.

Significance

Regenerative Medicine [RM], a strongly multidisciplinary field of endeavour, has the potential to greatly improve therapeutic outcomes for chronic illness and trauma, and subsequently to enhance afflicted individuals’ quality of life and capacity for physical activity. This will become increasingly important as populations, globally, age.

Many, perhaps all, industry and science leaders envision that, by synchronising shared aims and complementary knowledge and expertise of their respective sectors and by successfully carrying out the appropriate translational research and knowledge transfer, RM will find expression at a commercially relevant scale and stand to deliver affordable permanent solutions to those in need.

What is it?

Regenerative Medicine has been ‘defined’ in numerous ways. Any single definition is too restricting on what is a very diverse and fast-changing field. A better word might be ‘characterised’. Key characteristics are shown in the ovals in fig 1. The advance from ‘traditional’ medicine is shown in the block arrows.

A diagram showing the concept of regenerative medicine. Two bubbles, labelled \

Fig 1 Characterisation of Regenerative Medicine and its strategic mission

RM embraces: cell- and molecular-based therapies [replacement of compromised cells/tissue, stimulation of endogenous response, delivery of genetic or molecular therapies]; gene therapy [use of DNA as pharmaceutical agent to treat disease]; biologics and small molecules [stimulation of dormant or endogenous cells to regain their regenerative properties]; tissue engineering [TE: scaffolds created from synthetic and bio-based materials]; and biobanking [the collection, storage and distribution of bio-tissue].

The other field is stem cell biology. This is the study of unspecialised cells that can give rise to one or more different types of specialised cells. For instance, after adult marrow-derived Mesenchymal Stem Cells [MSCs] have divided, their progeny are capable of further division and differentiation into one of several mesenchymal phenotypes including osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, and adipocytes. That is, the original stem cells have the capability to differentiate into a variety of phenotypes and so provide the foundation for numerous potential therapies to treat chronic illnesses and traumatic injuries.

Further, it has become recognised that the beneficial effects of stem cells go further than those arising solely from differentiation viz

Stem cells can secrete combinations of trophic factors including cytokines and growth factors. These modulate, via paracrine action, the molecular composition of the environment to evoke responses from resident cells. MSCs, for instance, secrete bioactive factors that suppress the local immune system, inhibit fibrosis [scar formation] and apoptosis [‘normal’ or programmed cell death], enhance angiogenesis [blood vessel formation], and stimulate mitosis [division of a parent cell to produce two identical daughter cells] and differentiation of reparative cells or stem cells.

Researchers are working to understand such processes more fully and thus set the scene for innovative new therapies that will undoubtedly emerge. Further, the author suggests that future therapies may well, where ‘superior’ outcomes can be demonstrated and where regulatory requirements, not least for trophic factors’ Modes of Action, can be met, comprise an intimate combination of both differentiation-based mechanisms and trophic mechanisms.


1 Regenerative Medicine Industry Flag Waver and Associate Investigator with New Zealand’s Medical Technologies Core of Research Excellence [MedTechCoRE] regharris@xtra.co.nz