Stem cell therapy for chronic wounds: a concise literature review of recent clinical evidence

Chronic wounds diabetic foot ulcers (DFU), ischemic and venous ulcers, radiation and pressure injuries persist when inflammation, microvascular failure, and disordered cell signaling prevent normal repair. Standard care (sharp debridement, off-loading/compression, infection control, glycemic and nutrition management) is foundational, yet a subset of wounds remain “stalled.” Over the last decade, stem cell therapy particularly umbilical cord–derived mesenchymal stem cells (UC-MSCs) has been investigated as an adjunct to restore pro-healing biology. This literature review summarizes key designs, dosing approaches, outcomes, and safety signals from the attached clinical papers, with emphasis on terms patients and clinicians search for: chronic wounds, stem cell treatment, stem cell, and stem cell therapy.

Study designs and populations

The corpus spans a randomized, placebo-controlled pilot in long-standing chronic wounds of mixed etiologies; a phase I pilot in DFU with peripheral arterial disease (PAD) not amenable to revascularization; a CARE-guided case of a stage-IV pressure ulcer treated with Wharton’s jelly (WJ)–MSCs plus platelet-rich plasma (PRP); and a contemporary review aggregating a decade of clinical MSC wound studies, including DFU cohorts treated intra-arterially/intramuscularly and via topical scaffolds. The randomized pilot enrolled patients with nonhealing ulcers despite standard care and compared peri-wound UC-MSC placement to placebo; primary readouts included area reduction trajectories and microcirculatory indices over 1–4 weeks.

The DFU+PAD phase I study enrolled 14 patients and layered topical plus intravenous (IV) UC-MSC stem cell onto conservative management, following participants for short-term healing and up to three years for limb outcomes and safety. Dosing was 2×10^5 cells/kg per administration, capped at 1×10^7 cells.

The pressure-ulcer (PU) case used GMP-grade WJ-MSC stem cell combined with autologous PRP, documenting local tolerability and serial wound photography/measurements under CARE guidelines.

Finally, the Cell Journal review synthesized clinical experiences across burns, DFU, critical limb ischemia, and other complex wound states reporting routes, approximate doses, follow-up windows, and directionally consistent outcomes (perfusion gains, faster recovery, and higher closure rates).

Interventions and delivery (how stem cell treatment was used)

Delivery strategies varied with goals and anatomy:

  • Peri-wound/intradermal UC-MSC placement after debridement in the randomized trial targeting the wound edge where re-epithelialization initiates.
  • Topical + IV UC-MSCs in DFU+PAD aiming to influence systemic inflammatory tone while providing local trophic cues at the ulcer surface. The IV dose reflected common early-phase practice and respected an upper limit to standardize exposure.
  • WJ-MSCs + PRP for a complex PU leveraging PRP’s growth-factor burst (e.g., VEGF, PDGF, TGF-β) and provisional matrix to augment MSC stem cell paracrine activity and local persistence.

The broader clinical literature also includes intra-arterial and intramuscular routes for ischemic phenotypes and acellular scaffolds (e.g., amniotic membrane) carrying stem cells to the wound bed.

Efficacy outcomes

Randomized pilot (UC-MSC vs placebo) – By week 4, the stem cell therapy arm exhibited significantly greater wound-area reduction and higher day-to-day healing rates (days 1–14). Importantly, microcirculation improved at two weeks, with a marked increase in average blood perfusion and TcPO₂ relative to placebo signals consistent with transitioning from “stalled” inflammation to active granulation and epithelial advance.

DFU+PAD phase I (topical + IV UC-MSC stem cell) – Short-term healing was robust: >95% lesion-area closure within ~1.5 months for all patients, with improvements in Wagner grades, Rutherford categories, and pain scores. Imaging at 1.5 months did not show large-vessel revascularization, implying benefits were likely mediated through microcirculatory and immunomodulatory mechanisms rather than macro-arterial change an interpretation reinforced by the trial’s own discussion.

Pressure-ulcer case (WJ-MSCs + PRP) – The single-patient experience showed clinically meaningful granulation and re-epithelialization acceleration with WJ-MSC stem cell suspended in PRP, aligning with preclinical evidence that PRP + MSC stem cell increases proliferation, angiogenesis, and constructive remodeling. The authors highlight practical limits (n=1; measurement variance) and call for controlled comparisons vs standard care.

Ten-year clinical overview – The review table lists multiple small DFU cohorts and other ulcer entities where stem cell treatment (UC-MSC, BM-MSC, AD-MSC) was associated with enhanced blood flow, faster recovery, and higher healing rates over 1–3 months, with routes matched to phenotype (e.g., intra-arterial/intramuscular for ischemia).

Mechanistic signals (why stem cell therapy might work)

Across studies, improvements in TcPO₂, perfusion units, granulation quality, and early area regression suggest paracrine rather than engraftment-driven effects: UC-MSC stem cell modulate inflammatory tone, support endothelial sprouting and microvascular function, and encourage keratinocyte/fibroblast activity and matrix organization. These actions can be dynamic, with MSC secretomes shifting in response to local cues, but the precise spatiotemporal choreography in human wounds remains under active study.

Preclinical references within these papers reinforce the cell-free story: UC-MSC stem cell –conditioned media and extracellular vesicles can sometimes match or exceed the effect of transplanted cells on wound biology an observation that is motivating trials of exosome products as adjuncts in chronic wounds.

Safety profile

Across the included human studies and referenced syntheses, MSC therapy shows a favorable short-term safety signal. The DFU+PAD phase I reported only two transient fevers after IV infusion; no serious infusion reactions or organ complications were observed. A frequently cited meta-analysis of 36 prospective clinical trials found no association between MSC administration and acute infusion toxicity, organ complications, infection, death, or malignancy important context when counseling patients about stem cell treatment as an adjunct.

Limitations and heterogeneity

Notwithstanding promising signals, the literature remains heterogeneous. Trials vary in cell source (UC-MSC, BM-MSC, AD-MSC), dose (per-kg vs fixed), route (topical, intradermal, intra-arterial, IV), and outcomes (area change, perfusion, patient-reported symptoms, limb events). The PU case report underscores the need for controlled comparisons and standardized measurements, while the clinical review calls for protocol standardization and longer follow-up to confirm durability.

In the DFU+PAD pilot, absence of large-vessel change on early imaging reminds us that macro-revascularization is not the proximate mechanism; microcirculation metrics and symptom scales may be more sensitive to biologic change in this window.

Practical implications for care teams

For multidisciplinary wound programs contemplating stem cell therapy as an adjunct:

  1. Select the right phenotype – Chronicity ≥4–6 weeks despite standard care, evidence of inflammatory stall, and ischemic features that preclude further revascularization are common inclusion patterns. (Context from DFU/PAD phase I and randomized mixed-etiology cohorts.)
  2. Match route to goal – Peri-wound placement for edge biology; intramuscular/intra-arterial for ischemia; IV when systemic modulation is desired recognizing that early benefits track with perfusion and inflammatory indices, not large-artery anatomy.
  3. Monitor what moves first – Expect early changes in granulation quality, area regression, and microcirculatory metrics (TcPO₂, perfusion units) over 2–4 weeks, with patient-level improvements in pain and function as tissue matures.
  4. Maintain guardrails – Use GMP-grade products, sterile technique, and data-guided follow-up. Reinforce that stem cell treatment augments not replaces standard wound care. Calls for higher-quality randomized trials remain justified.

Conclusion

Across randomized, early-phase, and case-level evidence, stem cell therapy especially UC-MSC stem cell shows consistent early benefits in chronic wounds when layered onto best practice: faster area reduction, improved microcirculation (perfusion and TcPO₂), cleaner granulation, and symptom relief. Safety signals are reassuring in the short term. Heterogeneity in protocols warrants cautious interpretation and underscores the need for larger, well-controlled trials with standardized endpoints. For clinicians, the practical takeaway is to consider stem cell adjuncts in carefully selected patients and to track biologically sensitive markers granulation quality and microperfusion where the earliest benefits of stem cell treatment are most likely to appear.

Keywords: chronic wounds, stem cell treatment, stem cell, stem cell therapy, umbilical cord mesenchymal stem cells, UC-MSCs, diabetic foot ulcer, wound healing, TcPO₂, microcirculation.

References

Suzdaltseva Y, Zhidkih S, Kiselev SL, Stupin V. (2020). Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study. Stem Cells International, Article ID 5308609. doi:10.1155/2020/5308609.

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