Peripheral blood mononuclear cell secretome for tissue repair

Apoptosis, 2016 · DOI: 10.1007/s10495-016-1292-8 · Published: October 1, 2016

Simple Explanation

Cell-based therapies are being tested to regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors, known as the cell secretome, are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. The stem cell secretome has been commonly investigated in pre-clinical settings. Evidence suggests other cell types, like peripheral blood mononuclear cells (PBMCs), release biologically active paracrine factors that exert beneficial regenerative effects. The apoptotic PBMC secretome has been successfully used pre-clinically for the treatment of acute myocardial infarction, chronic heart failure, spinal cord injury, stroke, and wound healing.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Apoptotic PBMCs attenuated LPS-induced spillage of IL-6 and IL-1β in co-cultured monocytes and PBMCs. Irradiated PBMCs reduced T-cell proliferation.
2
The infusion of irradiated PBMC suspensions reduced infarct size compared to animals receiving non-irradiated PBMCs or cell culture medium alone. Functional parameters were improved in animals treated with apoptotic PBMC-S.
3
Apoptotic PBMC secretome exerts anti-inflammatory effects and reduce myocardial injury following AMI, and that the supernatants from these cells induce the expression of pro-angiogenic genes in vitro.

Research Summary

The use of human PBMCs as bioreactors for secretome-based therapies can be seen as an extension of the original concept of stem cell-based therapies to enable clinical applications. Using apoptotic PBMC-S instead of stem cells, we could promote tissue repair and regeneration in multiple pre-clinical indications with the identification of a variety of MOAs. The PBMC secretome may potentially revolutionize regenerative medicine when appropriate proof of concept studies in humans that meet the requirements of regulating agencies are finished.

Practical Implications

Therapeutic Potential

PBMC secretome-based therapies offer a readily available alternative to stem cell therapies for tissue repair and regeneration.

Clinical Translation

Clinical trials utilizing the PBMC secretome could provide proof-of-concept in humans for indications with unmet needs like diabetic foot ulcers, AMI, stroke, and spinal cord injury.

Commercialization Opportunities

Cooperation between clinically oriented scientists and blood banks could accelerate the inclusion of investors, as the certification of a validated GMP facility would result in significant (financial) risk reduction.

Study Limitations

1
The biologically active component(s) of the apoptotic PBMC secretome remain(s) to be fully identified.
2
The concentration(s) and mode(s) of delivery responsible for the effects of the PBMC secretome are not fully understood.
3
More detailed descriptions of the composition of exosomes, including exosomal lipids, mRNAs, miRNAs, proteins, and surface receptors, are needed.

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