Just Over the Horizon: Catheter Delivery of Stem Cell Therapy


Author

Cell type

Patients

Stroke type

Timeline for infusion

Pretreatment/infusion

Comments

Moniche F et al., Asturias, Spain [201]

Autologous CD34+ bone marrow cells

20

MCA infarct

5–9 days

None/intra-arterial

Phase I/II, single arm, evaluating safety and efficacy

Andre et al., Rio de Janeiro, Brazil [202]

Autologous BMMCs

12

MCA infarct

3 hours to 90 days

Intravenous/intra-arterial

Phase I, 2 arms (nonrandomized), evaluating safety

Completed, no safety issues

Habib et al., London, UK [203]

Autologous CD34+ bone marrow cells

10

Total anterior circulation infarct

Within 7 days

6 months to 5 years

None/Intra-arterial

Phase I/II, single arm, evaluating safety and tolerability

Currently recruiting

Aldagen, USA [207]

ALD 401 cells derived from autologous bone marrow

48

MCA infarct

Within 2 weeks

None/intra-arterial

Phase I/II, randomized, double blind, evaluating safety

Ongoing, currently recruited more than 25 patients

Morales V et al., Mexico

Autologous adipose-derived stromal cells

10

Ischemic and hemorrhagic stroke

None specified

None/intra-arterial

Open label, nonrandomized




 


2.

Endovascular approach

Most trials have targeted the MCA or distal internal carotid artery as the principal site of injection. The types of catheters and microcatheters used in these studies are not always reported. We believe that microcatheters should be studied for compatibility with the cell product. There had been initial concern that too small an inner diameter could lead to cell damage during the delivery process. Every clinical trial should complete validation runs to test for biocompatibility as part of regulatory requirements. Various catheters have been tested for their impact on cell viability [12, 27, 28]. However, the functional effects of catheter passage using different types of media and solutions are not very well defined. Our preliminary findings suggest that the media, catheter passage, and exposure to heparin/contrast can play a role in activating certain cytokines released from the cells, and these changes might lead to different functionality of the cells [28]. With regard to needles, based on published reports, it appears that one can use even a 26-gauge needle without damaging the cells [27].

 





Neurodegenerative Disorders


There are no large-scale trials using stand-alone endovascular approaches to deliver therapeutic cells in neurodegenerative disorders. There has been a randomized controlled trial of 33 patients with multisystem atrophy (MSA) in which MSCs were injected by intra-arterial and intravenous routes [29]. The trial suggested that MSA patients treated with MSCs had a delay in progression of their deficits compared with placebo. However, there were small ischemic lesions found on imaging in the intra-arterial group. Although the clinical significance is unknown, these findings validate concern that IA delivery of certain types of stem cells can cause tissue injury. Before expanding to new trials, further studies are needed to better understand the variables that contribute to tissue injury and how best to reduce these risks. There have also been a few reports of patients with Parkinson’s disease (PD) receiving stem cells by IA delivery [30], and a clinical trial is listed on clinicaltrials.gov testing autologous, adipose-derived MSCs by IV and IA routes for patients with PD.


Conclusion


In summary, endovascular delivery of cell-based therapies is currently at an early, investigational stage. A number of practical, scientific, and translational issues need to be better studied, but we anticipate that this mode of delivery will become a preferred approach in the future to administer cells for a wide range of neurological disorders.


References



1.

Ifejika-Jones NL, Barrett AM. Rehabilitation – emerging technologies, innovative therapies, and future objectives. Neurotherapeutics. 2011;8:452.PubMedCentralPubMedCrossRef


2.

Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res. 2011;109:923–40.PubMedCentralPubMedCrossRef


3.

Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res. 2003;92:692–9.PubMedCrossRef

Nov 3, 2016 | Posted by in NEUROLOGY | Comments Off on Just Over the Horizon: Catheter Delivery of Stem Cell Therapy

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