Culture of organized cell communities

doi:10.1016/S0169-409X(98)00017-9

Advanced Drug Delivery Reviews

Volume 33, Issues 1–2, 3 August 1998, Pages 15-30

https://doi.org/10.1016/S0169-409X(98)00017-9 Get rights and content

Abstract

Cells cultured in vitro will tend to retain their differentiated phenotype under conditions that resemble their natural in vivo environment, for example, when cultured on polymer scaffolds in tissue culture bioreactors. In this chapter, we define organized cell communities as three-dimensional in vitro grown cell–polymer constructs that display important structural and functional features of the natural tissue. We review representative studies in which the research goal was to culture organized cell communities resembling cartilage, bone, skeletal muscle or cardiac-like tissue. These constructs can potentially serve as tissue equivalents for in vivo transplantation or as a model system for the in vitro testing of cell and tissue-level responses to molecular, mechanical or genetic manipulations.

Introduction

The loss of a tissue or its function due to congenital defects, disease or trauma is one of the most difficult, frequent and costly problems in human medicine [52]. Current treatment modalities include autografts (e.g. skin, blood vessels), allografts (e.g. heart, kidney transplants) and artificial prostheses (e.g. joints, heart valves). However, each of the above methods has its limitations, which include shortage of donor tissue, immune rejection and pathogen transfer, and limited service life, respectively. The advent of tissue engineering has been motivated by the challenge to produce tissue substitutes that can restore the structural features and physiological functions of natural tissues in vivo [55].

There have been two basic approaches to tissue engineering: (a) in vitro cultivation of cell–polymer constructs for in vivo implantation and (b) direct in vivo implantation of isolated cells and/or biomaterials. We will discuss only the former category here, i.e. tissue constructs obtained by growing isolated cells on polymer scaffolds using various in vitro tissue culture bioreactors. We will define an organized cell community as an in vitro grown construct that displays important structural and functional characteristics of a natural tissue.

In addition to serving as tissue equivalents for clinical transplantation, organized cell communities can be used for in vitro studies of normal or pathological tissue function. In particular, constructs based on either normal or genetically engineered cells can be used to study cell differentiation and tissue formation under well controlled conditions, assess tissue responses to biochemical and mechanical stimuli and identify the functions of specific genes or gene products that can be either over-expressed or knocked-out. Organized cell communities thus represent a model system for the direct testing of cell and tissue-level responses to molecular, mechanical or genetic manipulations.

In the following review, we will discuss representative examples of organized cell communities as well as the effects of environmental factors on in vivo and in vitro tissue development.

Section snippets

Representative cultures of organized cell communities

Representative studies in which the research goal was to create in vitro a three-dimensional (3D) equivalent of cartilage, bone, skeletal muscle or cardiac muscle are listed in Table 1. These four tissue types were selected because the feasibility of culturing organized communities of their component cells has recently been demonstrated by independent research groups, and because their successful engineering is expected to have a major clinical impact. Several key parameters varied greatly from

Effects of environmental factors on tissue formation in vivo and in vitro

The structures and functions of cells, tissues and organs within the human body are in part determined by environmental factors. It is likely that the same factors that affect in vivo tissue development, maintenance and remodeling are important during the in vitro culture of organized cell communities. The selected examples described above (Section 2) suggest that at least two sets of factors can influence cell growth and differentiation in vitro: (1) scaffold-related factors, including spatial

Conclusion and future research directions

Over the last ten years, much progress has been made in the in vitro culture of organized cell communities for potential use as implants and/or studies of normal and pathological tissue function. This progress is due both to an improved understanding of in vivo tissue growth and the use of 3D scaffolds in conjunction with bioreactors to regenerate tissue equivalents from isolated cells.

We considered organized cell communities to be in vitro-grown 3D constructs that displayed important

Acknowledgements

This work was supported by the National Aeronautics and Space Administration (Grant No. NAG9-836).

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Culture of organized cell communities

Abstract

Introduction

Section snippets

Representative cultures of organized cell communities

Effects of environmental factors on tissue formation in vivo and in vitro

Conclusion and future research directions

Acknowledgements

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