Research Article
Intrinsic Variability Present in Wharton’s Jelly Mesenchymal
Stem Cells and T Cell Responses May Impact Cell Therapy
Fernanda Vieira Paladino,
1,2
Luiz Roberto Sardinha,
1
Carla Azevedo Piccinato,
1
and
Anna Carla Goldberg
1,2,3
1
Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
2
Departamento de Alergia e Imunopatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
3
Instituto de Investigação Em Imunologia-INCT, São Paulo, SP, Brazil
Correspondence should be addressed to Anna Carla Goldberg; goldberg@einstein.br
Received 10 February 2017; Accepted 26 April 2017; Published 5 July 2017
Academic Editor: Marc Hendrik Dahlke
Copyright © 2017 Fernanda Vieira Paladino et al. This 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.
Wharton’s jelly mesenchymal stem cells (WJ-MSC) exhibit immunomodulatory effects on T cell response. WJ-MSC are easy to
collect, process, and proliferate rapidly in culture, but information on the variability of individual cell samples impacting upon
in vitro expansion, immunomodulatory potential, and aging processes is still lacking. We propose to evaluate the
immunomodulatory cytokine profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to replicative
senescence in order to analyze if expected responses are affected. Our results show that the gene expression of
immunomodulatory molecules varied among samples with no specific pattern present. In coculture, all WJ-MSC were capable
of inhibiting mitogen-activated CD3
+
T cell proliferation, although to different degrees, and each PBMC responded with a
different level of inhibition. Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns of cytokine
mRNA expression and immunomodulatory capacity. We believe that variability between samples may play a role in the
effectiveness of WJ-MSC employed therapeutically.
1. Introduction
Mesenchymal stem cells (MSC) are multipotent cells
with the ability to proliferate, self-renew, and differenti-
ate into different cell types [1, 2]. Minimal criteria from
the International Society of Cellular Therapy establish
that human MSC must be plastic adherent, exhibit a
specific cell-surface expression profile, and differentiate
into osteocytes, adipocytes, and chondrocytes in vitro
[3, 4]. Bone marrow (BM) is deemed the “gold stan-
dard” for MSC derivation and use in clinical trials [5,
6]. However, MSC obtained from the umbilical cord
wall, known as Wharton’s jelly (WJ-MSC), can easily
be isolated and processed. The cells proliferate rapidly
in culture with the added value of being of very young
age (neonatal), environment protected, and from a
source with low ethical concerns.
Along with their capacity of differentiating into mesoder-
mal cells, MSC also display an important feature, namely,
their immunomodulatory capacity [7, 8]. Indeed, the current
consensus is that the more promising benefits occur in
patients presenting acute pathologies with a strong inflam-
matory component. In these conditions, in response to
proinflammatory cytokines, MSC start to produce immuno-
regulatory factors that downsize the immune response [9].
The effect is most likely due to soluble factors secreted by
the MSC [10], such as transforming growth factor β-1
(TGF-β1) [11], interleukin-10 (IL-10) [12], hepatocyte
growth factor (HGF) [13], prostaglandin E2 (PGE2) [14],
and indoleamine 2,3-dioxygenase- (IDO-) mediated trypto-
phan depletion [10], which result in crosstalk between MSC
and immune cells. The effects of MSC on the cells of the
immune system are usually anti-inflammatory and have been
observed on many cell types. MSC induce M1 to M2
Hindawi
Stem Cells International
Volume 2017, Article ID 8492797, 12 pages
https://doi.org/10.1155/2017/8492797