A 27-year-old male patient was referred to Yan’an Hospital affiliated of Kunming Medical University in November 2008, who was diagnosed as relapsing remitting MS and his Expanded Disability Status Scale (EDSS) were rose to 5. After he failed to show clinical improvement after 3 times of intravenous methylprednisolone (1g/day; IVMP) in total. He was enrolled in our clinical study, which approved by the ethics committee, and a written informed consent was obtained from the patient for being treated with multiple transfusions of MSCs. This clinical study aimed to exploring the effects and safety of mesenchymal stem cells transplantation for severe and refractory multiple sclerosis (MS).Initially the patient was infused with his bone marrow-derived stem cells, according to our previously published procedure[1]. From 2008 to January 2010, he received 3 intravenously as well as 3 intrathecal infusion of BM-MSCs.
As the patient stabilized, UC-MSCs were subsequently used for the transplantation. From August 2009 to December 2018, he received a total of 12 intravenous infusions of UC-MSCs, in absence of any other disease-modifying therapy (DMT). The isolation, culture methods and quality control of UC-MSCs used for this patient have been previously described [2].
From 2010 to 2016, UC-MSCs were obtained from voluntary donors attending the Yan’an Hospital affiliated of Kunming Medical University. In January 2016, the UC-MSCs source used for this patient changed as he became father, and thus the MSCs were harvested from the umbilical cord of his healthy baby. when his wife gave birth. Details of UC-MSCs infusion route, dosage and timepoints are shown in the Table 1. The patient remained well after the UC-MSCs therapy, showing only transient fatigue and drowsiness, immediately after the administration of MSCs. As indicated in Figure 2, his EDSS score decreased to 1.5 in 2013 and was maintained at that level until 2017. By 2018, his EDSS score was further reduced to 1.0, a drop of some 2.5 points, from the time he was first enrolled in our study. While we cannot exclude the possibility that the EDSS score improvement seen in this patient is due to a natural recovery, these data demonstrated that the multiple infusions of MSCs are probably quite safe and are possibly associated with anti-inflammatory effects. In this context, it is interesting to note that upon the cessation of the UC-MSCs during the second half of 2017, this patient relapse. By 2019, his EDSS score went from 1.0 (in 2018) to 3.5, the level at which he was enrolled in our study. These changes are in line with the MRI data which showed that in 2017, the T2-weighted positive abnormalities were decreased in number and size in the white matter as well as spinal cord(Figure 1). Moreover, it was noted that the edema around the lesions were reduced and some of the lesions had turned to an inactive status. However, by 2019, a number of new lesions appeared.
Table 1
Summary of MSCs treatment and EDSS score.
|
Date
|
MSC source
|
Route
|
Dose
|
EDSS score
|
Pre-treatment
|
06/09/2006
|
-
|
-
|
-
|
3.0
|
|
26/11/2008
|
BM-MSCs
|
iv
|
1.32×107
|
3.5
|
|
|
BM-MSCs
|
it
|
6.3×105
|
|
|
19/02/2009
|
BM-MSCs
|
iv
|
6.0×107
|
2.5
|
|
|
BM-MSCs
|
it
|
1.4×107
|
|
|
07/05/2009
|
BM-MSCs
|
iv
|
8.9×107
|
2.5
|
|
04/08/2009
|
UC-MSCs
|
iv
|
1.2×108
|
2.0
|
|
08/01/2010
|
BM-MSCs
|
it
|
1.47×105
|
2.0
|
|
29/08/2010
|
UC-MSCs
|
iv
|
3.27×108
|
2.0
|
|
22/04/2011
|
UC-MSCs
|
iv
|
1.4×108
|
2.0
|
|
29/12/2011
|
UC-MSCs
|
iv
|
1.51×108
|
2.0
|
|
04/09/2012
|
UC-MSCs
|
iv
|
8.65×107
|
2.0
|
|
22/09/2013
|
UC-MSCs
|
iv
|
1.07×108
|
1.5
|
|
15/01/2015
|
UC-MSCs
|
iv
|
1.66×108
|
1.5
|
|
06/01/2016
|
UC-MSCs
|
iv
|
9.1×107
|
1.5
|
|
21/04/2016
|
UC-MSCs
|
iv
|
5.09×107
|
1.5
|
|
22/07/2016
|
UC-MSCs
|
iv
|
9.32×107
|
1.5
|
|
28/03/2017
|
UC-MSCs
|
iv
|
1.03×108
|
1.5
|
|
22/09/2017
|
UC-MSCs
|
iv
|
7.0×107
|
1.5
|
Post-treatment
|
01/12/2018
|
-
|
-
|
-
|
1.0
|
Post-treatment
|
011/8/2019
|
-
|
-
|
-
|
3.5
|
MSCs: mesenchymal stem cells
BM-MSCs:bone marrow mesenchyml stem cells
UC-MSCs:umbilical cord mesenchymal stem cells
EDSS: Expanded Disability Status Scale
iv: intravenous injection
it: intrathecal injection