Human umbilical cord blood as a source of stem cells has recently been reported in experimental treatment of cerebral disorders. However, little is known about the nature of cells and cellular mechanisms leading to neurofunctional improvement. Here we investigated the potential of separated CD34+ versus CD34- human umbilical cord blood cells (HUCBC) to promote functional recovery following stroke. The experiments were performed in spontaneously hypertensive (SH) rats, known for a risk profile comparable to stroke patients

Boltze, Johannes

Buhrle, Christian

Egger, Dietmar

Emmrich, Frank

Geiger, Kathrin

Gunther, Albrecht

Kamprad, Manja

Kowalski, Ina

Reich, Doreen

English

PubMed

Obwohl humanes Nabelschnurblut als Quelle von Stammzellen für experimentelle Therapien von Erkrankungen des Zentralnervensystems derzeit intensiv untersucht wird, ist noch wenig über die zellulären Prozesse bekannt, die der funktionellen Verbesserung von Ausfallerscheinungen zugrunde liegen. In der vorliegenden Studie untersuchten wir das Potenzial humaner Nabelschnurblutzellen, funktionelle Verbesserungen nach einem experimentellen Schlaganfall zu unterstützen. Die Experimente wurden mit spontan hypertensiven (SH) Ratten durchgeführt, deren metabolische Grunderkrankungen dem Risikoprofil menschlicher Schlaganfallpatienten entsprechen. Nach drei Wochen der Konditionierung für die Verhaltenstests RotaRod und Beamwalk wurde ein experimenteller Schlaganfall durch permanente Okklusion der mittleren Hirnarterie (middle cerebral artery occlusion, MCAO) ausgelöst. Im Zuge der Zelltherapie wurden 1x106 kryokonservierte CD34+- oder CD34--Zellen 8 bis 10 Stunden nach Verschluss der rechten mittleren Hirnarterie intravenös appliziert. Die Verhaltenstests wurden zusammen mit der Erhebung des modified neurological severity score (mNSS) bis 29 Tage nach Eintritt des experimentellen Schlaganfalls durchgeführt, um die Entwicklung neurofunktionaler Defizite im Verlauf beurteilen und quantifizieren zu können. Dabei wurde eine annähernd komplette Rückbildung von Ausfallerscheinungen bei Gabe beider Zellpopulationen beobachtet. Um transplantierte Zellen lokalisieren zu können, wurden diese mit dem Fluoreszenzfarbstoff CFSE unmittelbar vor der systemischen Zellgabe markiert. Sowohl nach der Gabe von CD34+- als auch CD34--Zellen konnten CFSE-markierte Zellen in der Grenzzone zwischen zentraler Kolliquationsnekrose und funktionellem Hirngewebe detektiert werden. Immunhistologische Untersuchungen mit anti-CD68 Antikörpern gegen neuronale Marker (NF-L, Chromogranin) zeigten eine verstärkte Ansammlung von Zellen monozytärer Natur, während neuronale Zellen humanen Ursprungs nicht identifiziert werden konnten

Boltze, J.

Kowalski, I.

Geiger, K.

Reich, D.

Albrecht, G.

Buhrle, C.

Egger, D.

Kamprad, M.

Emmrich, F.

Fraunhofer-ePrints

Experimental treatment of stroke in spontaneously hypertensive rats by CD34+ and CD34- cord blood cells

Geiger, Kathrin D.

Reich, Doreen Melanie

Warwick Research Archives Portal Repository

Human umbilical cord blood as a source of stem cells has recently been reported in experimental treatment of cerebral disorders. However, little is known about the nature of cells and cellular mechanisms leading to neurofunctional improvement. Here we investigated the potential of separated CD34+ versus CD34- human umbilical cord blood cells (HUCBC) to promote functional recovery following stroke. The experiments were performed in spontaneously hypertensive (SH) rats, known for a risk profile comparable to stroke patients. After three weeks of behavioral training in the RotaRod and Beamwalk test arrays, stroke was induced by permanent middle cerebral artery occlusion (MCAO). For cell therapy, 1x106 cryopreserved cells were administered systemically between 8 and 10 hours after MCAO. The behavioral tests were performed together with a neurological severity score (mNSS) until day 29 to assess neurofunctional disabilities. Nearly complete functional remission was observed with both subpopulations CD34+ as well as CD34- cells. To localize cells histologically, they were labeled with a fluorescence dye (CFSE) before injection. Again, after administration of CD34+ as well as CD34- cells, CFSE labelled cells were found that accumulated in the border zone between the central necrosis of the ischemic lesion and functional brain tissue, thus indicating active attraction towards the lesion for both cell populations. Immunohistology with anti-CD68 and antibodies to human neuronal markers (NF-L, chromogranin) indicated an accumulation of human and rat monocytes in the border zone of the lesion while neuronal cells of human origin could not be detected in host brains

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Experimental treatment of stroke in spontaneously hypertensive rats by CD34+ and CD34- cord blood cells

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