Elsevier

Cytotherapy

Volume 20, Issue 2, February 2018, Pages 232-244
Cytotherapy

Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes

https://doi.org/10.1016/j.jcyt.2017.09.013Get rights and content
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Highlights

  • IM implantation represents a minimally invasive alternative to IV infusion that supports extended survival of MSCs.

  • Adult and neo-natal human MSCs can survive 5 months at an IM implantation site, but survive only 1–4 weeks when delivered IV, IP or SC.

  • Equivalent cell survival is observed for 3 days after IV, IP, SC or IM transplantation.

  • Survival potential can be recovered after cryopreservation, but diminishes with in vitro passage.

Abstract

Background

Mesenchymal stromal cells (MSCs) offer great potential for diverse clinical applications. However, conventional systemic infusion of MSCs limits their therapeutic benefit, since intravenously (IV) infused cells become entrapped in the lungs where their dwell time is short.

Methods

To explore possible alternatives to IV infusion, we used in vivo optical imaging to track the bio-distribution and survival of 1 million bioluminescent MSCs administered IV, intraperitoneally (IP), subcutaneously (SC) and intramuscularly (IM) in healthy athymic mice.

Results

IV-infused MSCs were undetectable within days of administration, whereas MSCs implanted IP or SC were only detected for 3 to 4 weeks. In contrast, MSCs sourced from human umbilical cord matrix or bone marrow survived more than 5 months in situ when administered IM. Long-term survival was optimally achieved using low passage cells delivered IM. However, MSCs could undergo approximately 30 doublings before their dwell time was compromised. Cryo-preserved MSCs administered IM promptly after thaw were predominantly cleared after 3 days, whereas equivalent cells cultured overnight prior to implantation survived more than 3 months.

Discussion

The IM route supports prolonged cell survival of both neo-natal and adult-derived MSCs, although short-term MSC survival was comparable between all tested routes up to day 3. IM implantation presents a useful alternative to achieve clinical benefits from prolonged MSC dwell time at a homeostatic implant site and is a minimally invasive delivery route suitable for many applications. However, optimized thaw protocols that restore full biological potential of cryo-preserved MSC therapies prior to implantation must be developed.

Key Words

bone marrow
cell survival
mesenchymal stromal cell
optical imaging
transplantation
umbilical cord

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