TY - JOUR

T1 - Efficacy of mesenchymal stem cell-delivery using perpendicular multi-needle injections to the skin

T2 - Evaluation of post-ejection cellular health and dermal delivery

AU - Rangatchew, Filip

AU - Rasmussen, Bo Sonnich

AU - Svalgaard, Jesper Dyrendom

AU - Haastrup, Eva

AU - Talman, Maj Lis M.

AU - Bonde, Christian

AU - Fischer-Nielsen, Anne

AU - Drzewiecki, Krzysztof T.

AU - Holmgaard, Rikke

AU - Munthe-Fog, Lea

N1 - Publisher Copyright: © 2022

PY - 2023

Y1 - 2023

N2 - Aim: Mesenchymal stem cell (MSC)-therapy is increasingly being evaluated in clinical trials. Dermal delivery is not only time consuming but also unreliable, potentially hampering the therapeutic result. Therefore, qualification of cell delivery protocols is essential. This study evaluated a clinically relevant automated multi-needle injection method for cutaneous MSC-therapy, allowing the skin to be readily and timely treated, by assessing both the cellular health post-ejection and dermal delivery. Methods: Following dispensation through the injector (31 G needles: 9- or 5-pin) the cellular health and potency (perceived- and long-term (12 h) viability, recovery, metabolism, adherence, proliferation and IDO1-expression) of adipose-derived stem cells (10–20–50 ×106 cells/ml) were assessed in vitro in addition to dermal delivery of solution in human skin. Results: No significant detrimental effect on the perceived cell viability, recovery, metabolism, adherence or IDO1-expression of either cell concentration was observed. However, the overall long-term viability and proliferation decreased significantly regardless of cell concentration, nonetheless marginally. An injection depth above 1.0 mm resulted in all needles piercing the skin with dermal delivery from up to 89% needles and minimal reflux to the skin surface, and the results were confirmed by ultrasound and histology. Conclusion: The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality.

AB - Aim: Mesenchymal stem cell (MSC)-therapy is increasingly being evaluated in clinical trials. Dermal delivery is not only time consuming but also unreliable, potentially hampering the therapeutic result. Therefore, qualification of cell delivery protocols is essential. This study evaluated a clinically relevant automated multi-needle injection method for cutaneous MSC-therapy, allowing the skin to be readily and timely treated, by assessing both the cellular health post-ejection and dermal delivery. Methods: Following dispensation through the injector (31 G needles: 9- or 5-pin) the cellular health and potency (perceived- and long-term (12 h) viability, recovery, metabolism, adherence, proliferation and IDO1-expression) of adipose-derived stem cells (10–20–50 ×106 cells/ml) were assessed in vitro in addition to dermal delivery of solution in human skin. Results: No significant detrimental effect on the perceived cell viability, recovery, metabolism, adherence or IDO1-expression of either cell concentration was observed. However, the overall long-term viability and proliferation decreased significantly regardless of cell concentration, nonetheless marginally. An injection depth above 1.0 mm resulted in all needles piercing the skin with dermal delivery from up to 89% needles and minimal reflux to the skin surface, and the results were confirmed by ultrasound and histology. Conclusion: The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality.

KW - Cell therapy

KW - Dermal delivery

KW - Injection

KW - Mesenchymal stem cell

KW - Regenerative medicine

KW - Skin therapy

U2 - 10.1016/j.burns.2022.04.020

DO - 10.1016/j.burns.2022.04.020

M3 - Journal article

C2 - 35618513

AN - SCOPUS:85130889744

VL - 49

SP - 633

EP - 645

JO - Burns

JF - Burns

SN - 0305-4179

IS - 3

ER -