Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

Abstract

Multiple sclerosis is a currently incurable inflammatory demyelinating syndrome. Recent reports suggest that bone marrow derived mesenchymal stem cells may have therapeutic potential in experimental models of demyelinating disease, but various alternative mechanisms, ranging from systemic immune effects to local cell replacement, have been proposed. Here we used intraperitoneal delivery of human mesenchymal stem cells to help test (a) whether human cells can indeed suppress disease, and (b) whether CNS infiltration is required for any beneficial effect. We found pronounced amelioration of clinical disease but profoundly little CNS infiltration. Our findings therefore help confirm the therapeutic potential of mesenchymal stem cells, show that this does indeed extend to human cells, and are consistent with a peripheral or systemic immune effect of human MSCs in this model. Keywords Mesenchymal stem cells; Multiple sclerosis; Experimental allergic encephalomyelitisMultiple sclerosis is an acquired inflammatory demyelinating syndrome of unknown cause, and which is currently incurable. In many individuals, progressive disability occurs during the course of the disease, as a consequence of irreversible CNS damage. The ineffectiveness of current therapies has emphasised the importance of novel treatment approaches, and stem cells are widely held as having particular promise.Bone marrow derived mesenchymal stem cells can proliferate substantially, and can differentiate into cells of all three germ cell layers, including neural cells; moreover they are relatively accessible, could be used for autologous therapy, and are capable of entering the CNS (particularly when damaged) from the circulation [6,11]. They are therefore considered good candidates for early clinical stem cell therapeutic studies.Recently, reports have appeared suggesting that bone marrow-derived cells can ameliorate toxic and inflammatory experimental demyelinating disease following intravenous delivery [1,3,5,7,[13][14][15][16]. However, whether this effect is achieved through cell replacement and

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…67 Several other studies confirmed the beneficial effect of MSCs injected systemically, 33,68 i.p. 69 or locally inside the CNS, 68 suggesting that not only do MSCs exert a potent inhibition of the autoimmune attack to the CNS but are also endowed with significant neuroprotective effects despite limited evidence of CNS infiltration (Figure 2). 16 It is noteworthy that neural stem cells 70 and, more recently, human embryonal stem cellderived neuronal precursor cells, 71 displayed a strikingly beneficial effect upon administration in EAE-affected mice through bystander mechanisms leading to the immunomodulation of autoreactivity and neuroprotection.…”

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

“…For example, MSC derived from adipose tissues or bone marrow have been used to treat experimental allergic encephalitis, inflammatory bowel disease, immune-mediated arthritis, airway inflammation, and graft-versus-host disease in rodent models [1,[9][10][11][12]. In addition, human MSC have been administered to rodent models of inflammatory diseases [13][14][15][16][17]. Thus, it is apparent that the immune modulatory properties of MSC can be utilized therapeutically in a number of different diseases settings.…”

The Use of Mesenchymal Stem Cells in the Treatment of Multiple Sclerosis: An Overview of Open Labels and Ongoing Studies

“…Gordon et al [39] used intra-peritoneal infusion of the hMSC to evaluate whether the CNS engraftment is a significant concern for treatment. They demonstrated an extensive improvement of clinical symptoms in EAE mice with little CNS infiltration.…”