18 research outputs found
Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial
This trial evaluated the feasibility and efficacy of the infusion of mesenchymal stem cells expanded using human serum for the treatment of refractory acute or chronic graft-versus-host disease. Twenty-eight expansions were started. In 22, a minimum of more than 1 x 10ⶠmesenchymal stem cells/kg were obtained after a median of 26 days; this threshold was not obtained in the remaining cases. Ten patients received cells for the treatment of refractory or relapsed acute graft-versus-host disease and 8 for chronic disease. One patient treated for acute graft-versus-host disease obtained a complete response, 6 had a partial response and 3 did not respond. One of the chronic patients achieved complete remision, 3 a partial response, and 4 did not respond. The current study supports the use of this approach in less heavily treated patients for both acute and chronic graft-versus-host disease. The trial has been registered at ClinicalTrials.gov: identifier NCT00447460
Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II)
Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety
and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized
clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect.
Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and
2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered
hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10Ă106
or 100Ă106
cultured autolâ
ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse
efects and clinical evolution, assessed using VAS and WOMAC scorings are reported.
Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminisâ
tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed
from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control
group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accordâ
ing to WOMAC. Control group showed an increase median value of 4 points (â11;10) while Low-dose and Highdose groups exhibited values of â18 (â28;â9) and â10 (â21;â3) points, respectively (Low-dose vs Control group
p=0.043). No clinical diferences between the BM-MSCs receiving groups were found.
Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proceâ
dure that results in long-term clinical and functional improvement of knee OA
Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: a randomized clinical trial with long-term follow-up
The aim of this clinical trial (ID Number NCT01803347) was to determine the safety
and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of
cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed
and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing
Spanish cell therapy network (TerCel): 15 years of successful collaborative translational research
In the current article we summarize the 15-year experience of the Spanish Cell Therapy Network (TerCel), a
successful collaborative public initiative funded by the Spanish government for the support of nationwide
translational research in this important area. Thirty-two research groups organized in three programs
devoted to cardiovascular, neurodegenerative and immune-inflammatory diseases, respectively, currently
form the network. Each program has three working packages focused on basic science, pre-clinical studies
and clinical application. TerCel has contributed during this period to boost the translational research in cell
therapy in Spain, setting up a network of Good Manufacturing Practice certified cell manufacturing facilities and increasing the number of translational research projects, publications, patents and clinical trials of
the participating groups, especially those in collaboration. TerCel pays particular attention to the public-private collaboration, which, for instance, has led to the development of the first allogeneic cell therapy product
approved by the European Medicines Agency, Darvadstrocel. The current collaborative work is focused on
the development of multicenter phase 2 and 3 trials that could translate these therapies to clinical practice
for the benefit of patients
Spanish cell therapy network (TerCel): 15 years of successful collaborative translational research
In the current article we summarize the 15-year experience of the Spanish Cell Therapy Network (TerCel), a
successful collaborative public initiative funded by the Spanish government for the support of nationwide
translational research in this important area. Thirty-two research groups organized in three programs
devoted to cardiovascular, neurodegenerative and immune-inflammatory diseases, respectively, currently
form the network. Each program has three working packages focused on basic science, pre-clinical studies
and clinical application. TerCel has contributed during this period to boost the translational research in cell
therapy in Spain, setting up a network of Good Manufacturing Practice certified cell manufacturing facilities and increasing the number of translational research projects, publications, patents and clinical trials of
the participating groups, especially those in collaboration. TerCel pays particular attention to the public-private collaboration, which, for instance, has led to the development of the first allogeneic cell therapy product
approved by the European Medicines Agency, Darvadstrocel. The current collaborative work is focused on
the development of multicenter phase 2 and 3 trials that could translate these therapies to clinical practice
for the benefit of patients
Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial
Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases.
Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.
Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10x10(6), 50x10(6) and 100x10(6) cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months.
Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months.
Conclusions:.
IGF-1 gene therapy to protect articular cartilage in a rat model of joint damage
Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs)
have shown benefit in other inflammatory diseases.
Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow
autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.
Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial
administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first
escalating-dose phase, three patients were included sequentially in three dose cohorts (10Ă106, 50Ă106 and
100Ă106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with
pulmonary function testing, 6-min walk test and St Georgeâs Respiratory Questionnaire was done at 1, 2, 3, 6
and 12 months, and with computed tomography at 3, 6 and 12 months.
Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from
treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before
treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events
were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial
decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at
3 months and three (23%) at 12 months.
Conclusions: The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in
IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic
instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous
MSCs in IPF patients
Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial
Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases.
Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.
Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10x10(6), 50x10(6) and 100x10(6) cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months.
Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months.
Conclusions:.
IGF-1 gene therapy to protect articular cartilage in a rat model of joint damage
Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs)
have shown benefit in other inflammatory diseases.
Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow
autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.
Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial
administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first
escalating-dose phase, three patients were included sequentially in three dose cohorts (10Ă106, 50Ă106 and
100Ă106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with
pulmonary function testing, 6-min walk test and St Georgeâs Respiratory Questionnaire was done at 1, 2, 3, 6
and 12 months, and with computed tomography at 3, 6 and 12 months.
Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from
treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before
treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events
were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial
decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at
3 months and three (23%) at 12 months.
Conclusions: The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in
IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic
instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous
MSCs in IPF patients
Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II)
Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety
and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized
clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect.
Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and
2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered
hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10Ă106
or 100Ă106
cultured autolâ
ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse
efects and clinical evolution, assessed using VAS and WOMAC scorings are reported.
Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminisâ
tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed
from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control
group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accordâ
ing to WOMAC. Control group showed an increase median value of 4 points (â11;10) while Low-dose and Highdose groups exhibited values of â18 (â28;â9) and â10 (â21;â3) points, respectively (Low-dose vs Control group
p=0.043). No clinical diferences between the BM-MSCs receiving groups were found.
Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proceâ
dure that results in long-term clinical and functional improvement of knee OA