Mesenchymal stem cell- mediated immunomodulation and the potential therapeutic application in Crohn’s Disease

Nadin Hawwash, Stephen M. Richardson


Mesenchymal stem cells (MSCs) are self-renewing stromal cells that possess a multipotent differentiation capacity as they can differentiate into numerous cell types such as adipose, bone and cartilage cells. MSCs have generated considerable interest for their remarkable tissue-reparative and immunomodulatory properties whereby MSCs can develop into functional cells at the injury site and control the body’s response to tissue damage respectively. Consequently, MSCs have vast therapeutic potential in treating Crohn’s disease (CD) which is a lifelong inflammatory bowel disease where tissue damage to a section of the gastrointestinal
tract occurs. The review aims to discuss the properties of MSCs and explore their potential application in treating CD. This review highlights the tissue-reparative properties of MSCs and specifically focuses on the immunomodulatory properties of MSCs. Results from clinical trials regarding the efficacy and safety of MSCs have been promising, proving that MSCs could potentially be used to treat CD.


stem cells; Crohn's disease; immunomodulation

Full Text:

Full text


NHS. Crohn's disease. Available from:

disease/ [Accessed 03 March 2019]

NHS. Treatment. Available from:

disease/treatment/ [Accessed 03 March 2019]

Jess T, Loftus E, Velayos F, Harmsen W, Zinsmeister A, Smyrk T et al. Risk

of intestinal cancer in inflammatory bowel disease: a population-based study

from olmsted county, Minnesota. Gastroenterology. 2006; 130(4): 1039-1046.

De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA,

Arias J et al. Immunosuppressive properties of mesenchymal stem cells:

advances and applications. Current Molecular Medicine. 2012; 12(5): 574-

Bassi Ê, Aita CA, Camara NO. Immune regulatory properties of multipotent

mesenchymal stromal cells: where do we stand? World Journal of Stem Cells.

; 3(1): 1.

Okamoto R, Watanabe M. Investigating cell therapy for inflammatory bowel

disease. Expert Opinion on Biological Therapy. 2016; 16(8): 1015-1023.

Friedenstein A, Piatetzky-Shapiro I, Petrakova K. Osteogenesis in transplants

of bone marrow cells. Development. 1966; 16(3): 381-390.

Friedenstein A, Chailakhjan R, Lalykina K. The development of fibroblast

colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.

Cell Proliferation. 1970; 3(4): 393-403.

Pittenger M, Mackay A, Beck S, Jaiswal R, Douglas R, Mosca J et al.

Multilineage potential of adult human mesenchymal stem cells. Science.

; 284(5411): 143-147.

Caplan A. Mesenchymal stem cells. Journal of Orthopaedic Research. 1991;

(5): 641-650.

Davies O, Smith A, Cooper P, Shelton R, Scheven B. The effects of

cryopreservation on cells isolated from adipose, bone marrow and dental pulp

tissues. Cryobiology. 2014; 69(2): 342-347.

Secunda R, Vennila R, Mohanashankar A, Rajasundari M, Jeswanth S,

Surendran R. Isolation, expansion and characterisation of mesenchymal stem

cells from human bone marrow, adipose tissue, umbilical cord blood and

matrix: a comparative study. Cytotechnology. 2014; 67(5): 793-807.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et

al. Minimal criteria for defining multipotent mesenchymal stromal cells. The

International Society for Cellular Therapy position statement. Cytotherapy.

; 8(4): 315-317.

Raynaud C, Maleki M, Lis R, Ahmed B, Al-Azwani I, Malek J et al.

Comprehensive characterization of mesenchymal stem cells from human

placenta and fetal membrane and their response to osteoactivin stimulation.

Stem Cells International. 2012; 2012: 1-13.

Duijvestein M, Vos A, Roelofs H, Wildenberg M, Wendrich B, Verspaget H et

al. Autologous bone marrow-derived mesenchymal stromal cell treatment for

refractory luminal Crohn's disease: results of a phase I study. Gut. 2010;

(12): 1662-1669.

Molendijk I, Bonsing B, Roelofs H, Peeters K, Wasser M, Dijkstra G et al.

Allogeneic bone marrow–derived mesenchymal stromal cells promote healing

of refractory perianal fistulas in patients with Crohn’s disease.

Gastroenterology. 2015; 149(4): 918-927.

Gao P, Zhou Y, Xian L, Li C, Xu T, Plunkett B et al. Functional effects of TGF-

on mesenchymal stem cell mobilization in cockroach allergen-induced

asthma. The Journal of Immunology. 2014; 192(10): 4560-4570.

Schrepfer S, Deuse T, Reichenspurner H, Fischbein M, Robbins R, Pelletier

M. Stem cell transplantation: the lung barrier. Transplantation Proceedings.

; 39(2): 573-576.

Han F, Wang C, Yang L, Zhan S, Zhang M, Tian K. Contribution of murine

bone marrow mesenchymal stem cells to pancreas regeneration after partial

pancreatectomy in mice. Cell Biology International. 2012; 36(9): 823-831.

Păunescu V, Deak E, Herman D, Siska I, Tanasie G, Bunu C et al. In vitro

differentiation of human mesenchymal stem cells to epithelial lineage. Journal

of Cellular and Molecular Medicine. 2007; 11(3): 502-8.

Ferrand J, Noël D, Lehours P, Prochazkova-Carlotti M, Chambonnier L,

Ménard A et al. Human bone marrow-derived stem cells acquire epithelial

characteristics through fusion with gastrointestinal epithelial cells. PLoS ONE.

; 6(5): e19569.

Szaraz P, Gratch Y, Iqbal F, Librach C. Differentiation of human

mesenchymal stem cells into functional cardiomyocyte-like cells. Journal of

Visualized Experiments. 2017; (126).

Nombela-Arrieta C, Ritz J, Silberstein L. The elusive nature and function of

mesenchymal stem cells. Nature Reviews Molecular Cell Biology. 2011;

(2): 126-131.

Qian H, Yang H, Xu W, Yan Y, Chen Q, Zhu W et al. Bone marrow

mesenchymal stem cells ameliorate rat acute renal failure by differentiation

into renal tubular epithelial-like cells. International Journal of Molecular

Medicine. 2008; 22(3): 325-332.

Cho K, Ju S, Cho S, Jung Y, Woo S, Seoh J et al. Mesenchymal stem cells

showed the highest potential for the regeneration of injured liver tissue

compared with other subpopulations of the bone marrow. Cell Biology

International. 2009; 33(7): 772-777.

Von Bahr L, Batsis I, Moll G, Hägg M, Szakos A, Sundberg B et al. Analysis of

tissues following mesenchymal stromal cell therapy in humans indicates

limited long-term engraftment and no ectopic tissue formation. Stem Cells.

; 30(7): 1575-1578.

Zhang S, Teo K, Chuah S, Lai R, Lim S, Toh W. MSC exosomes alleviate

temporomandibular joint osteoarthritis by attenuating inflammation and

restoring matrix homeostasis. Biomaterials. 2019; 200: 35-47.

Halim N, Aizat W, Yahaya B. The effect of mesenchymal stem cell-secreted

factors on airway epithelial repair. Regenerative Medicine. 2019; 14(1): 15-31.

Markovic B, Kanjevac T, Harrell C, Gazdic M, Fellabaum C, Arsenijevic N et

al. Molecular and cellular mechanisms involved in mesenchymal stem cell-

based therapy of inflammatory bowel diseases. Stem Cell Reviews and

Reports. 2017; 14(2): 153-165.

Gong W, Guo M, Han Z, Wang Y, Yang P, Xu C et al. Mesenchymal stem

cells stimulate intestinal stem cells to repair radiation-induced intestinal injury.

Cell Death & Disease. 2016; 7(9): e2387.

Soontararak S, Chow L, Johnson V, Coy J, Wheat W, Regan D et al.

Mesenchymal stem cells (MSC) derived from induced pluripotent stem cells

(IPSC) equivalent to adipose-derived MSC in promoting intestinal healing and

microbiome normalization in mouse inflammatory bowel disease model. Stem

Cells Translational Medicine. 2018; 7(6): 456-467.

Goessling W, North T, Loewer S, Lord A, Lee S, Stoick-Cooper C et al.

Genetic interaction of PGE2 and Wnt signaling regulates developmental

specification of stem cells and regeneration. Cell. 2009; 136(6): 1136-1147.

Sémont A, Demarquay C, Bessout R, Durand C, Benderitter M, Mathieu N.

Mesenchymal stem cell therapy stimulates endogenous host progenitor cells

to improve colonic epithelial regeneration. PLoS ONE. 2013; 8(7): e70170.

Chen H, Min X, Wang Q, Leung F, Shi L, Zhou Y et al. Pre-activation of

mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its

paracrine effects on radiation-induced intestinal injury. Scientific Reports.

; 3(5): 8718.

Chen X, Yan L, Guo Z, Chen Z, Chen Y, Li M et al. Adipose-derived

mesenchymal stem cells promote the survival of fat grafts via crosstalk

between the Nrf2 and TLR4 pathways. Cell Death & Disease. 2016; 7(9):


Tao H, Han Z, Han Z, Li Z. Proangiogenic features of mesenchymal stem

cells and their therapeutic applications. Stem Cells International. 2016; 2016:


Hayashi Y, Tsuji S, Tsujii M, Nishida T, Ishii S, Iijima H et al. Topical

implantation of mesenchymal stem cells has beneficial effects on healing of

experimental colitis in rats. Journal of Pharmacology and Experimental

Therapeutics. 2008; 326(2): 523-531.

Lee R, Pulin A, Seo M, Kota D, Ylostalo J, Larson B et al. Intravenous hMSCs

improve myocardial infarction in mice because cells embolized in lung are

activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell.

; 5(1): 54-63.

Martini F, Nath J, Bartholomew E. Fundamentals of anatomy & physiology.

th ed, pp778-804. San Francisco: Benjamin Cummings, 2018.

Shale M, Ghosh S. How intestinal epithelial cells tolerise dendritic cells and its

relevance to inflammatory bowel disease. Gut. 2009; 58(9): 1291-1299.

Ganz T. Epithelia: Not just physical barriers. Proceedings of the National

Academy of Sciences. 2002; 99(6): 3357-3358.

Newton K, Dixit V. Signalling in innate immunity and inflammation. Cold

Spring Harbor Perspectives in Biology. 2012; 4(3): a006049.

Crane J, Mongiardo K. Pro-inflammatory effects of uric acid in the

gastrointestinal tract. Immunological Investigations. 2013; 43(3): 255-266.

Matzinger P. The danger model: a renewed sense of self. Science. 2002;

(5566): 301-305.

Lawrence T. The nuclear factor NF- B Pathway in inflammation. Cold Spring

Harbor Perspectives in Biology. 2009; 1(6): a001651.

Porter C, Tribble D, Aliaga P, Halvorson H, Riddle M. Infectious gastroenteritis

and risk of developing inflammatory bowel disease. Gastroenterology. 2008;

(3): 781-786.

Palone F, Vitali R, Cucchiara S, Pierdomenico M, Negroni A, Aloi M et al.

Role of HMGB1 as a suitable biomarker of subclinical intestinal inflammation

and mucosal healing in patients with inflammatory bowel disease.

Inflammatory Bowel Diseases. 2014; 20(8): 1448-1457.

Huang Y, Chen Z. Inflammatory bowel disease related innate immunity and

adaptive immunity. American Journal of Translational Research. 2016; 8:


Nanini H, Bernardazzi C, Castro F, Souza H. Damage-associated molecular

patterns in inflammatory bowel disease: From biomarkers to therapeutic

targets. World Journal of Gastroenterology. 2018; 24(41): 4622-4634.

Oh J, Lee R, Yu J, Ko J, Lee H, Ko A et al. Intravenous mesenchymal stem

cells prevented rejection of allogeneic corneal transplants by aborting the

early inflammatory response. Molecular Therapy. 2012; 20(11): 2143-2152.

Yang H, Song W, Li Q, Kim S, Kim H, Ryu M et al. Canine mesenchymal stem

cells treated with TNF-α and IFN-γ enhance anti-inflammatory effects through

the COX-2/PGE2 pathway. Research in Veterinary Science. 2018; 119: 19-

Liu H, Kemeny D, Heng B, Ouyang H, Melendez A, Cao T. The

immunogenicity and immunomodulatory function of osteogenic cells

differentiated from mesenchymal stem cells. The Journal of Immunology.

; 176(5): 2864-2871.

Sheng H, Wang Y, Jin Y, Zhang Q, Zhang Y, Wang L et al. A critical role of

IFNγ in priming MSC-mediated suppression of T cell proliferation through up-

regulation of B7-H1. Cell Research. 2008; 18(8): 846-857.

Neurath M. IL-23 in inflammatory bowel diseases and colon cancer. Cytokine

& Growth Factor Reviews. 2019; 45: 1-8.

MacDonald T, Monteleone I, Fantini M, Monteleone G. Regulation of

homeostasis and inflammation in the intestine. Gastroenterology. 2011;

(6): 1768-1775.

Li Y, Zhang D, Xu L, Dong L, Zheng J, Lin Y et al. Cell–cell contact with

proinflammatory macrophages enhances the immunotherapeutic effect of

mesenchymal stem cells in two abortion models. Cellular & Molecular

Immunology. 2019.

Choi H, Lee R, Bazhanov N, Oh J, Prockop D. Anti-inflammatory protein TSG-

secreted by activated MSCs attenuates zymosan-induced mouse peritonitis

by decreasing TLR2/NF- B signaling in resident macrophages. Blood. 2011;

(2): 330-338.

Song W, Li Q, Ryu M, Ahn J, Bhang D, Jung Y et al. TSG-6 released from

intraperitoneally injected canine adipose tissue-derived mesenchymal stem

cells ameliorate inflammatory bowel disease by inducing M2 macrophage

switch in mice. Stem Cell Research & Therapy. 2018; 9(1): 91.

Li J, Xue H, Li T, Chu X, Xin D, Xiong Y et al. Exosomes derived from

mesenchymal stem cells attenuate the progression of atherosclerosis in

ApoE−/- mice via miR-let7 mediated infiltration and polarization of M2

macrophage. Biochemical and Biophysical Research Communications. 2019;

(4): 565-572.

François M, Romieu-Mourez R, Li M, Galipeau J. Human msc suppression

correlates with cytokine induction of indoleamine 2,3-dioxygenase and

bystander m2 macrophage differentiation. Molecular Therapy. 2012; 20(1):


Saldaña L, Bensiamar F, Vallés G, Mancebo F, García-Rey E, Vilaboa N.

Immunoregulatory potential of mesenchymal stem cells following activation by

macrophage-derived soluble factors. Stem Cell Research & Therapy. 2019;

(1): 58.

Nakajima M, Nito C, Sowa K, Suda S, Nishiyama Y, Nakamura-Takahashi A

et al. Mesenchymal stem cells overexpressing interleukin-10 promote

neuroprotection in experimental acute ischemic stroke. Molecular Therapy -

Methods & Clinical Development. 2017; 6: 102-111.

François M, Romieu-Mourez R, Li M, Galipeau J. Human MSC suppression

correlates with cytokine induction of indoleamine 2,3-dioxygenase and

bystander M2 macrophage differentiation. Molecular Therapy. 2012; 20(1):


Anderson P, Souza-Moreira L, Morell M, Caro M, O'Valle F, Gonzalez-Rey E

et al. Adipose-derived mesenchymal stromal cells induce immunomodulatory

macrophages which protect from experimental colitis and sepsis. Gut. 2012;

(8): 1131-1141.

Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the

innate immune system. Nature Reviews Immunology. 2012; 12(5): 383-396.

De Yang, Chen Q, Schmidt A, Anderson G, Wang J, Wooters J et al. Ll-37,

the neutrophil granule–and epithelial cell–derived cathelicidin, utilizes formyl

peptide receptor–like 1 (Fprl1) as a receptor to chemoattract human

peripheral blood neutrophils, monocytes, and T cells. The Journal of

Experimental Medicine. 2000; 192(7): 1069-1074.

Harbord M, Marks D, Forbes A, Bloom S, Day R, Segal A. Impaired neutrophil

chemotaxis in Crohn's disease relates to reduced production of chemokines

and can be augmented by granulocyte-colony stimulating factor. Alimentary

Pharmacology & Therapeutics. 2006; 24(4): 651-660.

Costa F. Calprotectin is a stronger predictive marker of relapse in ulcerative

colitis than in Crohn's disease. Gut. 2005; 54(3): 364-368.

Smith A, Rahman F, Hayee B, Graham S, Marks D, Sewell G et al.

Disordered macrophage cytokine secretion underlies impaired acute

inflammation and bacterial clearance in Crohn's disease. The Journal of

Experimental Medicine. 2009; 206(9): 1883-1897.

Zhu Q, Zhang X, Zhang L, Li W, Wu H, Yuan X et al. The IL-6–STAT3 axis

mediates a reciprocal crosstalk between cancer-derived mesenchymal stem

cells and neutrophils to synergistically prompt gastric cancer progression. Cell

Death & Disease. 2014; 5(6): 1295-1295.

Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F et

al. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for

neutrophil preservation in the bone marrow niche. Stem Cells. 2008; 26(1):


Leyendecker Jr. A, Pinheiro C, Amano M, Bueno D. The use of human

mesenchymal stem cells as therapeutic agents for the in vivo treatment of

immune-related diseases: a systematic review. Frontiers in Immunology.

; 9.

Li S, Zheng X, Li H, Zheng J, Chen X, Liu W et al. Mesenchymal stem cells

ameliorate hepatic ischemia/reperfusion injury via inhibition of neutrophil

recruitment. Journal of Immunology Research. 2018; 2018: 1-10.

Dyer D, Thomson J, Hermant A, Jowitt T, Handel T, Proudfoot A et al. TSG-6

inhibits neutrophil migration via direct interaction with the chemokine CXCL8.

The Journal of Immunology. 2014; 192(5): 2177-2185.

Li S, Zheng X, Li H, Zheng J, Chen X, Liu W et al. Mesenchymal stem cells

ameliorate hepatic ischemia/reperfusion injury via inhibition of neutrophil

recruitment. Journal of Immunology Research. 2018; 2018: 1-10.

Kim H, Yun J, Shin T, Lee S, Lee B, Yu K et al. Human umbilical cord blood

mesenchymal stem cell-derived PGE2and TGF-β1 alleviate atopic dermatitis

by reducing mast cell degranulation. Stem Cells. 2015; 33(4): 1254-1266.

Xu X, Rivkind A, Pikarsky A, Pappo O, Bischoff S, Levi‐Schaffer F. Mast cells

and eosinophils have a potential profibrogenic role in Crohn disease.

Scandinavian Journal of Gastroenterology. 2004; 39(5): 440-447.

Akers I, Parsons M, Hill M, Hollenberg M, Sanjar S, Laurent G et al. Mast cell

tryptase stimulates human lung fibroblast proliferation via protease-activated

receptor-2. American Journal of Physiology-Lung Cellular and Molecular

Physiology. 2000; 278(1): 193-201.

Adibe O, Georgeson K. Crohn's disease. Pediatric Surgery. 2012: 1209-1215.

Lee S, Ryu C, Shin J, Choi D, Kim A, Yu H et al. The therapeutic effect of

human embryonic stem cell-derived multipotent mesenchymal stem cells on

chemical-induced cystitis in rats. International Neurourology Journal. 2018;

: 34-45.

Kuwabara A, Liu J, Kamio Y, Liu A, Lawton M, Lee J et al. Protective effect of

mesenchymal stem cells against the development of intracranial aneurysm

rupture in mice. Neurosurgery. 2017; 81(6): 1021-1028.

Kawai T, Akira S. Pathogen recognition with toll-like receptors. Current

Opinion in Immunology. 2005; 17(4): 338-344.

Nauta A, Kruisselbrink A, Lurvink E, Willemze R, Fibbe W. Mesenchymal

stem cells inhibit generation and function of both CD34+-derived and

monocyte-derived dendritic cells. The Journal of Immunology. 2006; 177(4):


Rescigno M, Di Sabatino A. Dendritic cells in intestinal homeostasis and

disease. Journal of Clinical Investigation. 2009; 119(9): 2441-2450.

Djouad F, Charbonnier L, Bouffi C, Louis-Plence P, Bony C, Apparailly F et al.

Mesenchymal stem cells inhibit the differentiation of dendritic cells through an

interleukin-6-dependent mechanism. Stem Cells. 2007; 25(8): 2025-2032.

Spaggiari G, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-

derived DC maturation and function by selectively interfering with the

generation of immature DCs: central role of MSC-derived prostaglandin E2.

Blood. 2009; 113(26): 6576-6583.

Spaggiari G, Capobianco A, Abdelrazik H, Becchetti F, Mingari M, Moretta L.

Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and

cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin

E2. Blood. 2007; 111(3): 1327-1333.

El Haddad N, Moore R, Heathcote D, Mounayar M, Azzi J, Mfarrej B et al. The

novel role of SERPINB9 in cytotoxic protection of human mesenchymal stem

cells. The Journal of Immunology. 2011; 187(5): 2252-2260.

Ciccocioppo R, Cangemi G, Kruzliak P, Gallia A, Betti E, Badulli C et al. Ex

vivo immunosuppressive effects of mesenchymal stem cells on Crohn’s

disease mucosal T cells are largely dependent on indoleamine 2,3-

dioxygenase activity and cell-cell contact. Stem Cell Research & Therapy.

; 6(1).

Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel

disease. Journal of Clinical Investigation. 2007; 117(3): 514-521.

Chen Q, Yan L, Wang C, Wang W, Shi H, Su B et al. Mesenchymal stem cells

alleviate TNBS-induced colitis by modulating inflammatory and autoimmune

responses. World Journal of Gastroenterology. 2013; 19(29): 4702.

Sheng H, Wang Y, Jin Y, Zhang Q, Zhang Y, Wang L et al. A critical role of

IFNγ in priming MSC-mediated suppression of T cell proliferation through up-

regulation of B7-H1. Cell Research. 2008; 18(8): 846-857.

MacFarlane R, Graham S, Davies P, Korres N, Tsouchnica H, Heliotis M et al.

Anti-inflammatory role and immunomodulation of mesenchymal stem cells in

systemic joint diseases: potential for treatment. Expert Opinion on

Therapeutic Targets. 2013; 17(3): 243-254.

Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone

marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-

dioxygenase-mediated tryptophan degradation. Blood. 2004; 103(12): 4619-

Chen K, Wang D, Du W, Han Z, Ren H, Chi Y et al. Human umbilical cord

mesenchymal stem cells hUC-MSCs exert immunosuppressive activities

through a PGE2-dependent mechanism. Clinical Immunology. 2010; 135(3):


Hajkova M, Hermankova B, Javorkova E, Bohacova P, Zajicova A, Holan V et

al. Mesenchymal stem cells attenuate the adverse effects of

immunosuppressive drugs on distinct T cell subopulations. Stem Cell Reviews

and Reports. 2016; 13(1): 104-115.

Chiossone L, Conte R, Spaggiari G, Serra M, Romei C, Bellora F et al.

Mesenchymal stromal cells induce peculiar alternatively activated

macrophages capable of dampening both innate and adaptive immune

responses. Stem Cells. 2016; 34(7): 1909-1921.

Ge W, Jiang J, Arp J, Liu W, Garcia B, Wang H. Regulatory t-cell generation

and kidney allograft tolerance induced by mesenchymal stem cells associated

with indoleamine 2,3-dioxygenase expression. Transplantation. 2010; 90(12):


Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA

expression and immunologic properties of differentiated and undifferentiated

mesenchymal stem cells. Experimental Hematology. 2003; 31(10): 890-896.

Tse W, Pendleton J, Beyer W, Egalka M, Guinan E. Suppression of

allogeneic T-cell proliferation by human marrow stromal cells: implications in

transplantation. Transplantation. 2003; 75(3): 389-397.

Zhou B, Yue R, Murphy M, Peyer J, Morrison S. Leptin-receptor-

expressing mesenchymal stromal cells represent the main source of bone

formed by adult bone marrow. Cell Stem Cell. 2014; 15(2): 154-168.

Zhang J, Lv S, Liu X, Song B, Shi L. Umbilical cord mesenchymal stem

cell treatment for Crohn's disease: a randomized controlled clinical trial. Gut

and Liver. 2018; 12(1): 73-78.

Lightner A, Wang Z, Zubair A, Dozois E. A systematic review and

meta-analysis of mesenchymal stem cell injections for the treatment of

perianal Crohn’s disease. Diseases of the Colon & Rectum. 2018; 61(5): 629-

Caplan A. Adult mesenchymal stem cells for tissue engineering versus

regenerative medicine. Journal of Cellular Physiology. 2007; 213(2): 341-347.

Jia Z, Liang Y, Xu X, Li X, Liu Q, Ou Y et al. Isolation and

characterization of human mesenchymal stem cells derived from synovial fluid

by magnetic-activated cell sorting (MACS). Cell Biology International. 2017;

(3): 262-271.

Busser H, Najar M, Raicevic G, Pieters K, Velez Pombo R, Philippart

P et al. Isolation and Characterization of Human Mesenchymal Stromal Cell

Subpopulations: Comparison of Bone Marrow and Adipose Tissue. Stem

Cells and Development. 2015; 24(18): 2142-2157.


Copyright (c) 2020 Nadin Hawwash

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Manchester Open Library:
a partnership between Manchester University Press and The University of Manchester Library