Biomimetic platforms for human stem cell research

Abstract

Stem cells are central to developing new treatment options for tissue regeneration and constructing controllable models for biological research. Bioengineered cell culture environments that combine microenvironmental control with tissue-specific transport and signaling are critical tools in our efforts to study tissue development, regeneration, and disease under conditions that predict the human in vivo context. We propose that experimentation at the interfaces of biology, engineering, and medical sciences is critical for unlocking the full potential of stem cells. Here, we focus on the design and utilization of in vitro platforms that recapitulate the environments associated with tissue development, disease, and regeneration.

Figure 1. Bioengineering platforms

The work at the interface between stem cell science and bioengineering is now resulting in controllable models of high biological fidelity that are driving progress in three major areas: (i) new treatment modalities for regenerative medicine, (ii) study of development and disease, and (iii) fundamental biological research.

Figure 2. Biomimetic paradigm

Stem cell fate and function are regulated by the entire context of the cellular microenvironment (niche), through dynamic interactions of the cells with cascades of multiple factors: molecular, structural and physical. Native-like (biomimetic) cell environments can be engineered by a combined use of a scaffold (providing a structural and logistic template for cell differentiation and functional assembly) and a bioreactor (providing environmental control, molecular and physical signaling).

Figure 3. Scaffold-bioreactor systems for human stem cells

hESCs were cultured in porous alginate scaffolds using a rotating bioreactor (a) to form spatially defined EBs inside scaffold pores (b) An anatomically correct bone graft in the exact size and shape of a human temporomandibular joint condyle (reproduced with permission from Gerecht et al. 2004). (c) has been engineered by using an anatomically shaped decellularized bone scaffold (d) seeded with human mesenchymal stem cells and cultured with medium perfusion (e) in an “anatomical” bioreactor (panels c, d, e reproduced with permission from Grayson et al. 2009)