February 6, 2012 by

Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats—In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging

Neurosurgery:
February 2012 – Volume 70 – Issue 2 – p 435–444
doi: 10.1227/NEU.0b013e318230a795
Research-Animal

Osanai, Toshiya MD, PhD*; Kuroda, Satoshi MD, PhD*; Sugiyama, Taku MD, PhD*; Kawabori, Masahito MD*; Ito, Masaki MD*; Shichinohe, Hideo MD, PhD*; Kuge, Yuji PhD‡; Houkin, Kiyohiro MD, PhD*; Tamaki, Nagara MD, PhD‡; Iwasaki, Yoshinobu MD, PhD*

Abstract

BACKGROUND: A noninvasive and effective route of cell delivery should be established to yield maximal therapeutic effects for central nervous system (CNS) disorders.

OBJECTIVE: To elucidate whether intra-arterial delivery of bone marrow stromal cells (BMSCs) significantly promotes functional recovery in traumatic brain injury (TBI) in rats.

METHODS: Rat BMSCs were transplanted through the ipsilateral internal carotid artery 7 days after the onset of cortical freezing injury. The BMSCs were labeled with fluorescent dye, and in vivo optical imaging was employed to monitor the behaviors of cells for 4 weeks after transplantation. Motor function was assessed for 4 weeks, and the transplanted BMSCs were examined using immunohistochemistry.

RESULTS: In vivo optical imaging and histologic analysis clearly demonstrated that the intra-arterially injected BMSCs were engrafted during the first pass without systemic circulation, and the transplanted BMSCs started to migrate from the cerebral capillary bed to the injured CNS tissue within 3 hours. Intra-arterial BMSC transplantation significantly promoted functional recovery after cortical freezing injury. A subgroup of BMSCs expressed the phenotypes of neurons, astrocytes, and endothelial cells around the injured neocortex 4 weeks after transplantation.

CONCLUSION: Intra-arterial transplantation may be a valuable option for prompt, noninvasive delivery of BMSCs to the injured CNS tissue, enhancing functional recovery after TBI. In vivo optical imaging may provide important information on the intracerebral behaviors of donor cells by noninvasive, serial visualization.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , ,
February 3, 2012 by

Inhaling Stem Cells for Treating Parkinson’s

Danielyan et al. Rejuvenation Res.

Stem cells have been delivered in a variety of ways: intravenously, into the spinal canal (intrathecally), into the brain (stereotactically), into the joint (intra-articularly), and into the cardiac muscle (endocardially). Scientists from the Department of Clinical Pharmacology, University Hospital of Tübingen , Tübingen, Germany have reported today a new way of delivering stem cells: via the nose.

Previous experiments administering stem cells for the treatment of Parkinson’s were primarily aimed at injection directly into the brain using sterotactic methods. These methods are highly invasive and there is always the potential of causing injury. Additionally some groups have used intravenous administration but the washout and number of cells being stuck in the lung and liver was reported as a potential problem.

The promise of using stem cells for the treatment of Parkinson’s comes not only from the direct regenerative ability of stem cells such as mesenchymal stem cells, but also from the fact that Parkinson’s is associated with inflammatory cytokine production, which has been previously demonstrated to be inhibited by stem cell administration.

Intranasal administration of bone marrow mesenchymal stem cells was performed in rats induced to develop a Parkinson’s like disease in which the dopaminergic cells were killed by administration of the toxin 6-hydroxydopamine (6-OHDA).

In rats that received the stem cells intranasally it was possible to find stem cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10(6) MSCs applied intranasally, 24% of the stem cells could be detected for least 4.5 months in the brains of 6-OHDA rats. It appears that the stem cells administered actually could proliferate in vivo as shown by expression of proliferating cell nuclear antigen on the administered mesenchymal stem cells.

Functionally it appeared that the intranasal administration increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase apoptotic cells as detected by TUNEL. Decreases in dopamine were prevented by cellular administration. A decrease in the inflammatory cytokines TNF, IFN-g, IL-2, 2, 6, and 12 was observed to be associated with the administration of cell therapy.

It will be interesting to see if this easy to apply technique will enter clinical trials. Already clinical trials are using non-conventional means of stem cell administration, for example the topical application of stem cells for burn wounds, which is being performed by Dr. Amit Patel from the University of Utah, who we interviewed for the Cellmedicine news blog above.

Filed Under: News, Parkinson's, Stem Cell Research Tagged With: , , , , , , ,
April 30, 2011 by

Bone Marrow Stem Cells Protect Lungs from Herbicide Injury

Yang et al. Clin Toxicol (Phila). 2011 Apr;49(4):298-302.
Paraquat is a herbicide that is linked to development of Parkinsons. It also is a toxin to lung cells and is used as a model of inducing lung injury in rats. In the current study the investigators wanted to see if administration of bone marrow mesenchymal stem cells had a therapeutic effect on paraquat-induced lung injury in rats.
The investigators used 54 female SD rats that were randomly divided into four groups:
a) Paraquat treated group,
b) Paraquat and bone marrow mesenchymal stem cell treated group,
c) Bone marrow mesenchymal stem cell alone treated group
d) Control untreated group
The stem cells were injected intravenously and animals were sacrificed 14 days after injection.
While animals receiving paraquat alone lived an averaty of 9.6 days, all rats receiving bone marrow mesenchymal stem cells lived more than 14 days. Bone marrow mesenchymal stem cell treatment was associated with less wet lung, decreases in plasma IL-1 and TNF-alpha, decrease in MDA, and decrease in NF-kappa B. Upregulated levels of the antioxidant enzyme superoxide dismutase was observed.
The ability to stimulate repair of the lung by mesenchymal stem cells is not new. Previous studies have shown that mesenchymal stem cells are capable of reducing endotoxin induced lung injury by secretion of keratinocyte growth factor. Other studies have shown that mesenchymal stem cells produce interleukin 1 receptor antagonist in the bleomycine induced model of lung fibrosis.
As with other stem cell therapies described on this website, there is some controversy as to the biological mechanisms by which the stem cells are mediating their therapeutic effect. One possibility is that they are secreting growth factors that stimulate proliferation of endogenous stem cells that are already resident in the lung. The other possibility is that the stem cells are directly differentiating into lung tissue.

Filed Under: Kidney and Lung, News, Stem Cell Research Tagged With: , , , ,