Original Article
Modulatory and regenerative potential of transplanted bone
marrow-derived mesenchymal stem cells on rifampicin-induced
kidney toxicity
Lawal Danjuma
a, b
, Pooi Ling Mok
c, d, n
, Akon Higuchi
e, f, g
, Rukman Awang Hamat
a
,
Seoh Wei Teh
c
, Avin Ee-Hwan Koh
c
, Murugan A. Munusamy
g
, Palanisamy Arulselvan
h
,
Mariappan Rajan
i
, Arivudai Nambi
j
, K.B. Swamy
j
, Kiruthiga Vijayaraman
k
,
Kadarkarai Murugan
l
, Kalimuthusamy Natarajaseenivasan
m
,
Suresh Kumar Subbiah
a, d, o, *
a
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor,
Malaysia
b
Department of Microbiology and Biotechnology, Faculty of Science, Federal University Duste, P.M.B 7156, Duste, Jigawa, Nigeria
c
Department of Biomedical Science, Faculty of Medicine and Health Science Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
d
Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
e
Department of Chemical and Materials Engineering, National Central University, Jhong-li, Taoyuan, 32001, Taiwan
f
Department of Reproduction, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan
g
Department of Botany and Microbiology, King Saud University, Riyadh,11451, Saudi Arabia
h
Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
i
Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai,
625 021, Tamil Nadu, India
j
Faculty of Medicine, Lincoln University College, Malaysia
k
Department of Medical Biotechnology, Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, International Medical
University, Malaysia
l
Division of Entomology, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
m
Medical Microbiology Laboratory, Department of Microbiology, Centre of Excellence in Life Sciences, Bharathidasan University, Tiruchirappalli, India
n
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, P.O. Box 2014, Sakaka, Aljouf Province, Saudi Arabia
o
Muthayammal Centre for Advanced Research, Muthayammal College of Arts and Science, Rasipuram, Namakkal, Tamil Nadu, 637408, India
article info
Article history:
Received 16 August 2018
Accepted 3 September 2018
Keywords:
Stem cell therapy
Mesenchymal stem cells
Rifampicin
Tuberculosis
Histopathology
Kidney
abstract
Introduction: Anti-tuberculosis agent rifampicin is extensively used for its effectiveness. Possible com-
plications of tuberculosis and prolonged rifampicin treatment include kidney damage; these conditions
can lead to reduced efficiency of the affected kidney and consequently to other diseases. Bone marrow-
derived mesenchymal stem cells (BMMSCs) can be used in conjunction with rifampicin to avert kidney
damage; because of its regenerative and differentiating potentials into kidney cells. This research was
designed to assess the modulatory and regenerative potentials of MSCs in averting kidney damage due to
rifampicin-induced kidney toxicity in Wistar rats and their progenies. BMMSCs used in this research
were characterized according to the guidelines of International Society for Cellular Therapy.
Methods: The rats (male and female) were divided into three experimental groups, as follows: Group 1:
control rats (4 males & 4 females); Group 2: rats treated with rifampicin only (4 males & 4 females); and
Group 3: rats treated with rifampicin plus MSCs (4 males & 4 females). Therapeutic doses of rifampicin
(9 mg/kg/day for 3-months) and MSCs infusions (twice/month for 3-months) were administered orally
and intravenously respectively. At the end of the three months, the animals were bred together to
determine if the effects would carry over to the next generation. Following breeding, the rats were
sacrificed to harvest serum for biochemical analysis and the kidneys were also harvested for histological
analysis and quantification of the glomeruli size, for the adult rats and their progenies.
Results: The results showed some level of alterations in the biochemical indicators and histopathological
damage in the rats that received rifampicin treatment alone, while the control and stem cells treated
* Corresponding author. Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences Universiti Putra Malaysia, 43400, Serdang,
Selangor, Malaysia.
E-mail address: sureshkudsc@gmail.com (S.K. Subbiah).
Peer review under responsibility of the Japanese Society for Regenerative Medicine.
Contents lists available at ScienceDirect
Regenerative Therapy
journal homepage: http://www.elsevier.com/locate/reth
https://doi.org/10.1016/j.reth.2018.09.001
2352-3204/© 2018, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Regenerative Therapy 9 (2018) 100e110