Advancements in cell-based therapies for the treatment of pressure injuries: A systematic review of interventional studies

Abstract

The high recurrence and complications associated with severe pressure injuries (PI) necessitate the exploration of advanced treatments, such as cell-based therapies, to facilitate wound healing. Such techniques harness the ability of different cell types to promote angiogenesis, re-epithelialization of the skin, and tissue regeneration. This systematic review explores the efficacy of cell-based therapies and tissue engineering in treating deep PI. We searched for interventional studies using cells in the treatment of PI in adults in four online libraries (PubMed, Embase, Ovid Medline, and Cochrane; latest search 10th June 2023). We found one randomized clinical trial (RCT), two non-RCT, and three pre-post studies, comprising 481 study participants with PI (253 intervention/228 controls). The risk of bias was categorized as moderate due to minimal bias in outcome measurements, or high owing to unclear patient randomization methods, as assessed by the ROBINS-I, NIH, and RoB-2 tools. Four cell types were identified in the context of cell-based therapies of PI: bone marrow mononuclear stem cells (BM-MNCs, n = 2); hematopoietic derived stem cells (HSC, n = 1); macrophages and activated macrophage suspensions (AMS, n = 2); and cryopreserved placental membrane containing viable cells (vCPM, n = 1). Wound healing outcomes were observed in patients undergoing cell-based therapies, including complete wound closure (AMS, vCPM; n = 142), faster healing rate (BM-MNCs, AMS; n = 146), improved granulation tissue formation (HSC, n = 3) and shorter hospitalization time (BM-MNCs; n = 108) compared to standard of care, with no adverse reactions. PI healing rate decreased only in one study with BM-MNC therapy, compared to control (n = 86). Based on the available data, though with limited evidence, it seems that macrophage deployment showed the most favorable outcomes. The results indicate that cell-based therapies offer a potential avenue for enhancing wound healing and tissue repair in PI; however, more extensive research is needed in this domain.

Keywords: Pressure injuries; cell-based therapies; systematic review; wound healing.

Figure 1.

This diagram illustrates the potential sites (shown as red spots) of pressure injury occurrence in wheelchair and bed-ridden individuals ((a) possible sites of pressure injury occurrence). It also shows the various stages of PI progression from the mildest (grade I) to the most severe (grade IV) cases ((b) progression of pressure injury degeneration). In this review we included only pressure injuries from grade III to grade IV. Source: Diagram adapted from https://www.kentcht.nhs.uk/leaflet/pressure-ulcer-prevention/.

Figure 2.

PRISMA flow diagram shows the process of inclusion and screening of studies for treatment of pressure injuries which involve cells. The flowchart illustrates the steps taken during searches of databases, screening, and reasons for exclusion.

Figure 3.

Diagram summarizing the various cell types that have been used in therapeutic approaches to treat deep pressure injuries (PI). These include bone marrow-derived mononuclear cells (BM-MNCs), hematopoietic derived stem cells (HSCs), placental membrane containing viable cells (vCPM) and macrophages and activated macrophages suspension (AMS). Research has shown that when patients undergo cell-based therapies utilizing these cell types, positive results are observed in regards to number of complete wound closures, faster healing rate, shorter hospitalization, and in most of the case no reported recurrence of the injuries. Only one study reported increased PI recurrence with BM-MNC treatment after a period of 1 year. Notably, cells isolated from the bone marrow and placenta have resulted in encouraging structural improvements to the degenerated tissue, whereas macrophages have been effective in modulating the underlying inflammatory state of pressure injuries. (Outcomes are identified as positive (+), uninfluential (o) and negative (−)).