The presence of mesenchymal progenitor cells (MPCs) in rheumatoid arthritis (RA) articular cartilage is sparsely investigated largely owing to the persistent pathogenic disease condition and lack of specific biomarkers. Considering the recent advancements for potential cell-based therapies in immunomodulatory diseases, such as RA, this in vitro study was aimed at investigating the cellular, molecular, and differentiation characteristics of human RA cartilage-derived MPCs. Articular cartilage fragments from RA patients were obtained for the isolation of MPCs and characterization of their cellular and biological properties, cytogenetic stability, pluripotency, and plasticity. Established MPCs were phenotypically identified using a panel of markers, and their differentiation ability into mesenchymal lineages was assessed by cytochemical staining and the expression of molecular markers. MPCs displayed a heterogenous population of cells with characteristic features of multipotent stem cells. Cells had higher viability, proliferative rate, and colony-forming ability. Further, MPCs showed the expression of pluripotency markers, cytogenetic stability, and minimal replicative senescence. In addition, MPCs differentiated into osteocytes, adipocytes, and chondrocytes, and modulated the expression of each lineage-specific gene markers. The results demonstrated the availability of a viable pool of MPCs residing in RA cartilage, which could serve as an ideal cell source for reinstating native homotypic cartilage.

1.
Aletaha
D
,
Neogi
T
,
Silman
AJ
,
Funovits
J
,
Felson
DT
,
Bingham
CO
3rd
,
.
2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative
.
Ann Rheum Dis
.
2010 Sep
;
69
(
9
):
1580
8
.
2.
Alsalameh
S
,
Amin
R
,
Gemba
T
,
Lotz
M
.
Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage
.
Arthritis Rheum
.
2004 May
;
50
(
5
):
1522
32
.
3.
Arai
F
,
Ohneda
O
,
Miyamoto
T
,
Zhang
XQ
,
Suda
T
.
Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation
.
J Exp Med
.
2002 Jun
;
195
(
12
):
1549
63
.
4.
Dominici
M
,
Le Blanc
K
,
Mueller
I
,
Slaper-Cortenbach
I
,
Marini
F
,
Krause
D
,
.
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement
.
Cytotherapy
.
2006
;
8
(
4
):
315
7
.
5.
Edilova
MI
,
Akram
A
,
Abdul-Sater
AA
.
Innate immunity drives pathogenesis of rheumatoid arthritis
.
Biomed J
.
2021 Apr
;
44
(
2
):
172
82
.
6.
Fattahi
R
,
Mohebichamkhorami
F
,
Taghipour
N
,
Keshel
SH
.
The effect of extracellular matrix remodeling on material-based strategies for bone regeneration: Review article
.
Tissue Cell
.
2022 Jun
;
76
:
101748
.
7.
Fellows
CR
,
Williams
R
,
Davies
IR
,
Gohil
K
,
Baird
DM
,
Fairclough
J
,
.
Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
.
Sci Rep
.
2017 Feb
;
7
:
41421
.
8.
Furukawa
H
,
Oka
S
,
Shimada
K
,
Hashimoto
A
,
Tohma
S
.
Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis
.
J Hum Genet
.
2015 Nov
;
60
(
11
):
691
6
.
9.
Ghoryani
M
,
Shariati-Sarabi
Z
,
Tavakkol-Afshari
J
,
Ghasemi
A
,
Poursamimi
J
,
Mohammadi
M
.
Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran
.
Biomed Pharmacother
.
2019 Jan
;
109
:
1834
40
.
10.
Grau-Vorster
M
,
Laitinen
A
,
Nystedt
J
,
Vives
J
.
HLA-DR expression in clinical-grade bone marrow-derived multipotent mesenchymal stromal cells: a two-site study
.
Stem Cell Res Ther
.
2019 Jun
;
10
(
1
):
164
.
11.
Hu
N
,
Gao
Y
,
Jayasuriya
CT
,
Liu
W
,
Du
H
,
Ding
J
,
.
Chondrogenic induction of human osteoarthritic cartilage-derived mesenchymal stem cells activates mineralization and hypertrophic and osteogenic gene expression through a mechanomiR
.
Arthritis Res Ther
.
2019 Jul
;
21
(
1
):
167
.
12.
Jacob
J
,
Aggarwal
A
,
Aggarwal
A
,
Bhattacharyya
S
,
Kumar
V
,
Sharma
V
,
.
Senescent chondrogenic progenitor cells derived from articular cartilage of knee osteoarthritis patients contributes to senescence-associated secretory phenotype via release of IL-6 and IL-8
.
Acta Histochem
.
2022 Apr
;
124
(
3
):
151867
.
13.
Jayasuriya
CT
,
Hu
N
,
Li
J
,
Lemme
N
,
Terek
R
,
Ehrlich
MG
,
.
Molecular characterization of mesenchymal stem cells in human osteoarthritis cartilage reveals contribution to the OA phenotype
.
Sci Rep
.
2018 May
;
8
(
1
):
7044
.
14.
Jiang
Y
,
Cai
Y
,
Zhang
W
,
Yin
Z
,
Hu
C
,
Tong
T
,
.
Human cartilage-derived progenitor cells from committed chondrocytes for efficient cartilage repair and regeneration
.
Stem Cells Transl Med
.
2016 Jun
;
5
(
6
):
733
44
.
15.
Jiang
Z
,
Yu
S
,
Lin
H
,
Bi
R
.
Expression and function of cartilage-derived pluripotent cells in joint development and repair
.
Stem Cell Res Ther
.
2020 Mar
;
11
(
1
):
111
.
16.
Karamini
A
,
Bakopoulou
A
,
Andreadis
D
,
Gkiouras
K
,
Kritis
A
.
Therapeutic potential of mesenchymal stromal stem cells in rheumatoid arthritis: A systematic review of in vivo studies
.
Stem Cell Rev Rep
.
2020 Apr
;
16
(
2
):
276
87
.
17.
Kim
YH
,
Yoon
DS
,
Kim
HO
,
Lee
JW
.
Characterization of different subpopulations from bone marrow-derived mesenchymal stromal cells by alkaline phosphatase expression
.
Stem Cells Dev
.
2012 Nov
;
21
(
16
):
2958
68
.
18.
Kohno
Y
,
Mizuno
M
,
Ozeki
N
,
Katano
H
,
Komori
K
,
Fujii
S
,
.
Yields and chondrogenic potential of primary synovial mesenchymal stem cells are comparable between rheumatoid arthritis and osteoarthritis patients
.
Stem Cell Res Ther
.
2017 May
;
8
(
1
):
115
.
19.
Li
G
,
Zheng
B
,
Meszaros
LB
,
Vella
JB
,
Usas
A
,
Matsumoto
T
,
.
Identification and characterization of chondrogenic progenitor cells in the fascia of postnatal skeletal muscle
.
J Mol Cell Biol
.
2011 Dec
;
3
(
6
):
369
77
.
20.
Lopez-Santalla
M
,
Fernandez-Perez
R
,
Garin
MI
.
Mesenchymal stem/stromal cells for rheumatoid arthritis treatment: An update on clinical applications
.
Cells
.
2020 Aug
;
9
(
8
):
1852
.
21.
Manjappa
A
,
Rao
S
,
Shetty
S
,
Shetty
V
,
Asode
A
,
Shetty
M
,
.
Characterization of human articular cartilage derived mesenchymal progenitor cells from osteoarthritis patients
.
J Adv Biotechnol Exp Ther
.
2021 Jan
;
4
(
2
):
200
9
.
22.
Mazor
M
,
Cesaro
A
,
Ali
M
,
Best
TM
,
Lespessaille
E
,
Toumi
H
.
Progenitor Cells from Cartilage: Grade Specific Differences in Stem Cell Marker Expression
.
Int J Mol Sci
.
2017 Aug
;
18
(
8
):
1759
.
23.
Minashima
T
,
Kirsch
T
.
Annexin A6 regulates catabolic events in articular chondrocytes via the modulation of NF-κB and Wnt/β-catenin signaling
.
PLoS One
.
2018 May
;
13
(
5
):
e0197690
.
24.
O'Conor
CJ
,
Case
N
,
Guilak
F
.
Mechanical regulation of chondrogenesis
.
Stem Cell Res Ther
.
2013 Jul
;
4
(
4
):
61
.
25.
Okamura
G
,
Ebina
K
,
Hirao
M
,
Chijimatsu
R
,
Yonetani
Y
,
Etani
Y
,
.
Promoting effect of basic fibroblast growth factor in synovial mesenchymal stem cell-based cartilage regeneration
.
Int J Mol Sci
.
2020 Dec
;
22
(
1
):
300
.
26.
Ostrowska
M
,
Maśliński
W
,
Prochorec-Sobieszek
M
,
Nieciecki
M
,
Sudoł-Szopińska
I
.
Cartilage and bone damage in rheumatoid arthritis
.
Reumatologia
.
2018
;
56
(
2
):
111
20
.
27.
Pei
M
,
Luo
J
,
Chen
Q
.
Enhancing and maintaining chondrogenesis of synovial fibroblasts by cartilage extracellular matrix protein matrilins
.
Osteoarthritis Cartilage
.
2008 Sep
;
16
(
9
):
1110
7
.
28.
Prideaux
M
,
Wright
CS
,
Noonan
ML
,
Yi
X
,
Clinkenbeard
EL
,
Mevel
E
,
.
Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation
.
Sci Rep
.
2021 Nov
;
11
(
1
):
22593
.
29.
Rios
HF
,
Ye
L
,
Dusevich
V
,
Eick
D
,
Bonewald
LF
,
Feng
JQ
.
DMP1 is essential for osteocyte formation and function
.
J Musculoskelet Neuronal Interact
.
2005 Oct-Dec
;
5
(
4
):
325
7
.
30.
Robert
AW
,
Marcon
BH
,
Dallagiovanna
B
,
Shigunov
P
.
Adipogenesis, osteogenesis and chondrogenesis of human mesenchymal stem/stromal cells: a comparative transcriptome approach
.
Front Cell Dev Biol
.
2020 Jul
;
8
:
561
.
31.
Robinson
D
,
Hasharoni
A
,
Cohen
N
,
Yayon
A
,
Moskowitz
RM
,
Nevo
Z
.
Fibroblast growth factor receptor-3 as a marker for precartilaginous stem cells
.
Clin Orthop Relat Res
.
1999 Oct
;
367
(
367 Suppl l
):
S163
75
.
32.
Sandrasaigaran
P
,
Algraittee
SJR
,
Ahmad
AR
,
Vidyadaran
S
,
Ramasamy
R
.
Characterisation and immunosuppressive activity of human cartilage-derived mesenchymal stem cells
.
Cytotechnology
.
2018 Jun
;
70
(
3
):
1037
50
.
33.
Schminke
B
,
Trautmann
S
,
Mai
B
,
Miosge
N
,
Blaschke
S
.
Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage
.
Eur J Immunol
.
2016 Feb
;
46
(
2
):
440
5
.
34.
Schrobback
K
,
Wrobel
J
,
Hutmacher
DW
,
Woodfield
TB
,
Klein
TJ
.
Stage-specific embryonic antigen-4 is not a marker for chondrogenic and osteogenic potential in cultured chondrocytes and mesenchymal progenitor cells
.
Tissue Eng A
.
2013 Jun
;
19
(
11‐12
):
1316
26
.
35.
Williams
R
,
Khan
IM
,
Richardson
K
,
Nelson
L
,
McCarthy
HE
,
Analbelsi
T
,
.
Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage
.
PLoS One
.
2010 Oct
;
5
(
10
):
e13246
.
36.
Xue
K
,
Zhang
X
,
Gao
Z
,
Xia
W
,
Qi
L
,
Liu
K
.
Cartilage progenitor cells combined with PHBV in cartilage tissue engineering
.
J Transl Med
.
2019 Mar
;
17
(
1
):
104
.
You do not currently have access to this content.