**6. Conclusions**

Extensive progress has been made in the last years concerning cell therapy for sepsis and ARDS. Cell therapies have shown promising results in pre-clinical

*Innovations in Cell Research and Therapy*

**12**

**Study title** Adipose-derived mesenchymal stem cells in acute

respiratory distress syndrome

Russian clinical trial of mesenchymal cells in patients with

NCT01849237 NCT01775774

ARDS

MSC

Phase 1/2a

1 or 5 or 10 million

July 2013

February 2018

USA

[102, 108]

cells/kg

NCT02097641

NCT02421484

Sepsis

MSC

Phase 1

0.3 or 1 or 3 million

May 2015

June 2017

Canada

[103]

cells/kg

Sepsis

MSC

Phase 1/2

1–2 millions/kg/day

December 2012

May 2015

Russia

[109]

intravenous

septic shock and severe neutropenia

Human mesenchymal stem cells for acute respiratory

distress syndrome (START)

Cellular immunotherapy for septic shock: a phase I trial

Treatment of severe acute respiratory distress syndrome

NCT02215811

ARDS

MSC

Phase 1

Not known. Cells

March 2014

December 2015

Sweden

are combined with

ECMO

with allogeneic bone marrow-derived mesenchymal

Human umbilical cord-derived mesenchymal stem cell

NCT02444455 NCT02611609 NCT02883803 NCT02804945

ARDS

MSC

Phase 2

3 × 106 cell/kg

February 2017

February 2019

USA

intravenous

Sepsis

MSC

Phase 1

106/kg intravenous

December 2016

December 2019

France

ARDS

Multistem

Phase 1/2

Not known

January 2016

November

USA/UK

2018

(MSC)

ARDS

MSC

Phase 1/2

5 × 105/kg intravenous

May 2015

December 2017

China

therapy in acute lung injury (UCMSC-ALI)

A phase 1/2 study to assess MultiStem® therapy in acute

respiratory distress syndrome (MUST-ARDS)

Effects of administration of mesenchymal stem cells on

organ failure during the septic shock (CSM choc)

Mesenchymal stem cells (MSCs) for treatment of

acute respiratory distress syndrome (ARD) in stem cell

Repair of acute respiratory distress syndrome by stromal

NCT03042143

ARDS

MSC

Phase 1/2

2 doses, not specified

2017

2020

September

September

UK

cell administration (REALIST)

**Table 2.**

*Phase 1 and phase 2 clinical studies with cell therapies for ARDS and sepsis (adapted from reference X).*

transplant patients

stromal cells

(CISS)

**Register number**

**Sepsis/**

**Cell type**

**Phase**

**Dose and via**

**Start date**

**Finish date**

**Country**

**Reference**

**ARDS**

NCT01902082

ARDS

MSC

Phase 1

1 × 106 intravenous

2012

2014

November

November

China

[104]

studies. Several pathways, proteins, miRNAs, and lipids have been characterized and explain the mechanism of action of these cell therapies.

Several questions need further study, including determining the best source for the MSCs isolation, their large-scale production, and cryopreservation. Moreover, the therapeutic potential of MSCs and its conditioned media need to be studied for checking their efficacy in short-term and long-term follow-up studies.

The heterogeneity of patients with sepsis and ARDS is enormous, and establish a target population or the stratification of the patients will help us to determine better the therapeutic effect of these therapies.

There are many complications and concerns with using stem cells for cell-based therapy. The future may emphasis on the stimulation of other cells (growth factors, cytokines, and various other hematopoietic elements) that facilitate the formation or repair of endothelium and epithelium and the modulation of inflammatory cells.

We need to await evidence that these cell therapies have a benefit in patients with sepsis or ARDS and evaluate the phase I and II results from the ongoing studies.
