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What?
Microcarriers are small, solid, or porous particles that are used in various fields, including cell therapy and biotechnology. Essentially, microcarriers are tiny beads ranging in size from 100 to 300 microns. They are typically made of biocompatible materials such as polystyrene, dextran, gelatin, or solubilizing material such as cross-linked polyglycolic acid (PGA).

When? 
The purpose of the microcarrier is to provide a larger surface area for cell attachment, allowing expansion capacity to be amplified several fold compared to traditional flat cultures. Instead of being cultivated on a flat surface, cells are cultured on the surface of spherical microcarriers that remain in suspension during stirring, with each microcarrier carrying hundreds of cells. 

Who?
Today, there are many researchers working with three dimensional microcarrier systems for MSC culture in a variety of fields, including regenerative medicine. The earliest successful MSC microcarrier expansion was reported only in 2007 by Frauenschuh and collaborators (1). Rafiq and collaborators performed a systematic review on 13 commercially available microcarriers to define an “ideal microcarrier”, and illustrated that the performance of the microcarriers when stirred was consistently better than when they were static (2). The SoloHill plastic microcarrier was chosen as the optimal microcarrier for human MSC expansion due to its xeno-free formulation, processing capability, and the ability to effectively harvest cells from the microcarrier in spinner flasks without compromising cellular immunophenotype and differentiation capacity. Pinto and collaborators described the use of plastic microcarriers in a vertical wheel bioreactor system to scale up adipose and umbilical cord matrix-derived MSCs (3). More recently, Miguel and collaborators described a serum-/xeno-free microcarrier-based culture system in a Vertical-Wheel^TM bioreactor (VWBR) that enabled the scalable production of MSC-derived extracellular vesicles (MSC-EVs) (4). Another useful resource for microcarrier research was written by Koh and collaborators who systematically reviewed three dimensional (3D) microcarrier systems in MSC culture, highlighting 14 articles that used microcarriers for MSC expansion (5).

Where? How? 

There is a pressing need for scalable culture systems for MSCs due to the large number of cells required in clinical applications. MSCs are increasingly utilized for a myriad of clinical applications ranging from intrathecal treatment of spinal cord injury to incorporation into an implantable biosynthetic matrix to treat anal fistulas. MSCs can be isolated from various sources such as bone marrow, adipose tissue, and umbilical cord blood, and can be expanded in vitro for clinical applications. Bioreactors are widely used to culture MSCs on a large scale, and microcarriers enable the culture of anchorage‐dependent cells in stirred‐tank bioreactors (6). Microcarriers are also a convenient solution for producing vaccines and other biologics, including exosomes.

Here, we will discuss the different types of microcarriers used for MSC production with bioreactors, common commercially available microcarriers, and preferred xeno-free and GMP-grade microcarriers. Our lab had experience with Synthemax II (Corning) dissolvable microcarriers easily dissociated by EDTA & pectinase and, later, Star Plus microcarriers (SoloHill by Sartorius) that are xeno-free, GMP-grade, and come in a sterile, ready-to-use formulation that requires final filtration steps.

Non-Porous Microcarriers

Non-porous microcarriers are made of materials such as polystyrene or glass, and have a smooth surface that facilitates cell attachment. These microcarriers are typically used for adherent cells such as MSCs, and provide a stable surface for cell attachment, allowing for cell growth and proliferation. Non-porous microcarriers are easy to manufacture, have a high yield, and can be sterilized easily, making them ideal for large-scale production of MSCs.

Porous Microcarriers

Porous microcarriers are composed of a non-toxic, biocompatible material, such as collagen or gelatin. These microcarriers have a highly porous structure, which provides a larger surface area for cell attachment and nutrient exchange. The high porosity allows cells to attach into the inner part of the microcarrier and facilitates efficient mass transfer of oxygen and nutrients, promoting cell growth and proliferation.

Because of the high surface area-to-volume ratio of microcarrier systems, cell yield per unit culture medium volume is high. Furthermore, by adjusting the microcarrier concentration and adding fresh microcarriers, this technology allows for easy adjustment of the surface area available for cell development and bead-to-bead transfer of expanding cells.

Table. 1 Commercially available microcarriers suitable for use in the 3D milieu of Bioreactors.