Research Article
Attachment, Growth, and Detachment of Human Mesenchymal
Stem Cells in a Chemically Defined Medium
Denise Salzig,
1
Jasmin Leber,
1
Katharina Merkewitz,
1
Michaela C. Lange,
1
Natascha Köster,
1
and Peter Czermak
1,2,3,4
1
Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen,
35390 Giessen, Germany
2
Faculty of Biology and Chemistry, Justus Liebig University, 35390 Giessen, Germany
3
Project Group Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), 35394 Giessen, Germany
4
Department of Chemical Engineering, Kansas State University, Manhattan, KS 66506, USA
Correspondence should be addressed to Denise Salzig; denise.salzig@lse.thm.de
Received 8 October 2015; Revised 18 January 2016; Accepted 26 January 2016
Academic Editor: Tao-Sheng Li
Copyright © 2016 Denise Salzig et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Te manufacture of human mesenchymal stem cells (hMSCs) for clinical applications requires an appropriate growth surface and
an optimized, preferably chemically defned medium (CDM) for expansion. We investigated a new protein/peptide-free CDM that
supports the adhesion, growth, and detachment of an immortalized hMSC line (hMSC-TERT) as well as primary cells derived from
bone marrow (bm-hMSCs) and adipose tissue (ad-hMSCs). We observed the rapid attachment and spreading of hMSC-TERT cells
and ad-hMSCs in CDM concomitant with the expression of integrin and actin fbers. Cell spreading was promoted by coating the
growth surface with collagen type IV and fbronectin. Te growth of hMSC-TERT cells was similar in CDM and serum-containing
medium whereas the lag phase of bm-hMSCs was prolonged in CDM. FGF-2 or surface coating with collagen type IV promoted the
growth of bm-hMSCs, but laminin had no efect. All three cell types retained their trilineage diferentiation capability in CDM and
were detached by several enzymes (but not collagenase in the case of hMSC-TERT cells). Te medium and coating did not afect
detachment efciency but infuenced cell survival afer detachment. CDM combined with cell-specifc surface coatings and/or
FGF-2 supplements is therefore as efective as serum-containing medium for the manufacture of diferent hMSC types.
1. Introduction
Human mesenchymal stem/stromal cells (hMSCs) are ofen
used for cell therapy because they ofer many advantageous
characteristics [1]. Before therapeutic use, hMSCs must be
expanded to produce the number of cells needed per patient
and per dose (at least 1-2 × 10
6
hMSCs per kg) [2]. Te growth
of hMSCs is anchorage-dependent, and the interactions
among the growth surface, cells, and surrounding medium
are therefore important for the manufacture of suitable
numbers of healthy cells.
Cell adhesion is necessary for hMSC expansion and is
driven by both nonspecifc and specifc interactions.
Rounded cells in suspension initially attach to the surface due
to complementary electrostatic/ionic forces and the growth
surface then interacts with cell surface integrins, the
principal receptors mediating cell-matrix adhesion [3].
Integrin activation results in the formation of heterodimers,
which initiate signaling cascades that activate downstream
genes and ultimately regulate cell morphology and behavior.
Te cell fattens and spreads due to the activation of protein
kinase C (PKC) and the subsequent accumulation of focal
adhesion kinase (FAK) and actin flaments at the leading
edges of the cells. Te completion of cell spreading and strong
adhesion to the surface, which is required for proliferation,
is characterized by the inactivation of PKC and the cross-
linking of actin to defned intracellular stress fbers along
with FAK located at the focal adhesion sites. Te actin forms
a stable cytoskeleton, which maintains the cell in its adherent
spread state [4, 5].
Hindawi Publishing Corporation
Stem Cells International
Volume 2016, Article ID 5246584, 10 pages
http://dx.doi.org/10.1155/2016/5246584