What question did this study set out to answer?

This research aims to explore the potential of hematopoietic stem cells engineered to deliver Angiotensin-(1-7) for stroke recovery.

January 10, 2026Acta Neurobiologiae Experimentalis0 citationsOpen Access

Hematopoietic stem cell‑based angiotensin‑(1‑7) delivery to the brain improves functional outcomefollowing cerebral ischemia

AAAqeela AfzalThe University of Sydney FDFiona DeslandMount Sinai Hospital HLHongwei LiBeijing Institute of Fashion Technology

Key Result

Hematopoietic stem cells transduced with Angiotensin‑(1‑7) improved post-stroke outcomes, reducing behavioral deficits on the Bederson scale in a rat model.

Key Points

This research aims to explore the potential of hematopoietic stem cells engineered to deliver Angiotensin-(1-7) for stroke recovery.
Utilized a rat model of cerebral ischemia for experimentation.
Involved three groups: Stroke + PBS, Stroke + HSC, Stroke + Ang-(1-7)-transduced HSC.
Administered bone marrow-derived HSCs transduced with lentivirus containing Ang-(1-7).
Conducted neurological assessments 72 hours after treatment.
Ang-(1-7) transduced HSCs secreted the peptide effectively for 72 hours post-infection in vitro.
Stroked rats treated with Ang-(1-7) infected HSC showed a reduction in behavioral deficits on the neurological assessment scale.
The findings indicate improved post-stroke outcomes via HSC-mediated Ang-(1-7) delivery.

Structured PICO

Does intra-arterial delivery of Angiotensin-(1-7) transduced hematopoietic stem cells improve neurological deficits and reduce infarct size in a rat model of cerebral ischemia?

Population

Male Sprague-Dawley rats (250-275 g) subjected to Endothelin-1 induced middle cerebral artery occlusion (MCAO). Total n=82 (48 used as bone marrow donors, 20 for the MCAO stroke model, and 14 for in vitro RNA analysis).

Intervention

1 million hematopoietic stem cells (HSC) transduced via a lentivirus with Angiotensin-(1-7) suspended in 200 μl PBS, delivered intra-arterially immediately after MCAO.

Comparator

Intra-arterial delivery of 200 μl PBS alone, or 1 million non-transduced HSC in 200 μl PBS.

Outcome

Neurological deficits assessed by the Bederson neurological assessment scale at 72 hours post-surgery.surrogate

In a rat model of cerebral ischemia, intra-arterial delivery of hematopoietic stem cells genetically modified to overexpress Angiotensin-(1-7) significantly improved short-term neurological deficits, demonstrating a novel biologic delivery mechanism for neurotherapeutics.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Angiotensin‑(1‑7) Ang‑(1‑7) exerts physiological effects in the brain mediated by its receptor, Mas. Recent studies have successfully demonstrated that Ang‑(1‑7) exerts neuroprotective effects following cerebral ischemia in a rat model. However, prior investigations utilized direct intracerebral cannulation for Ang‑(1‑7) delivery, potentially limiting human application. Hematopoietic stem cells (HSC) have been previously demonstrated to mobilize to the site of cerebral injury in response to stroke. Therefore, we sought to examine the therapeutic potential of HSC transduced via a lentivirus with Ang‑(1‑7) to migrate to the ischemic hemisphere and overexpress Ang‑(1‑7) following stroke. Animals were divided into 3 groups: Stroke + PBS, Stroke + HSC, Stroke + Ang‑(1‑7)‑transduced HSC. Bone marrow from separate animals was harvested and used for injection of the HSC, with or without lentivirus induced Ang‑(1‑7) transduction. A neurological assessment was performed at 72 hours post‑surgery. Ang‑(1‑7) transduced HSC secreted the peptide up to 72 hours post infection, in vitro. Stroked animals injected with the Ang‑(1‑7) infected HSC exhibited reduced behavioral deficits on the Bederson neurological assessment scale. These data suggest that HSC‑mediated delivery of Ang‑(1‑7) to ischemic brain appears to improve post‑stroke outcomes and may offer a novel route of therapeutic agent delivery to the brain.

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