1. 2025;28;S1-S119Comprehensive Evidence-Based Guidelines for Regenerative Therapies in the Management of Chronic Low Back Pain: 2025 Update from the American Society Of Interventional Pain Physicians (ASIPP)
   Guidelines
   Laxmaiah Manchikanti, MD, Riya Navani, ., Annu Navani, MD, Mahendra Sanapati, MD, Alan D. Kaye, MD, PhD, Adam M. Kaye, PharmD, Amol Soin, MD, Devi Nampiaparampil, MD, Kenneth D. Candido, MD, Alaa Abd-Elsayed, MD, Theodore T. Sand, PhD, Navneet Boddu, MD, Sairam Atluri, MD, Anss Annie Augustine, BDS, Dajie Wang, MD, John Santa Ana, DO, Lady Christine Ong Sio, MD, Vidyasagar Pampati, MSc, Michael Khadavi, MD, Nebojsa Nick Knezevic, MD, PhD, Robert Farhat, DO, Shivam S. Shah, MD, Shounuck J. Patel, DO, Tom Nabity, Jr, MD, Alexander Bautista, MD, Aaron K. Calodney, MD, Joseph Cabaret, MD, Miles R. Day, MD, Paul J. Christo, MD, Sanjay Bakshi, MD, Shalini Shah, MD, Sheldon Jordan, MD, Sheri L. Albers, DO, Vivek Manocha, MD, and Joshua A. Hirsch, MD.

BACKGROUND: Regenerative medicine is an evolving medical subspecialty dedicated to enhancing the body’s natural healing mechanisms to repair or replace damaged tissues. By using autologous or allogeneic biologics, it offers the potential to restore function where conventional therapies have shown limited success. While this field holds great promise and continues to generate enthusiasm among both patients and clinicians, it remains in early stages of clinical validation. Therefore, it must be approached with careful optimism and responsible application, ensuring that its presentation, promotion, and use in clinical settings are grounded in evidence and ethical standards.

OBJECTIVE: To provide updated, evidence-based recommendations for the role of regenerative therapies in managing moderate to severe chronic low back pain.

METHODS: A multidisciplinary panel of experts, convened by the American Society of Interventional Pain Physicians (ASIPP), systematically reviewed the current evidence and incorporated patient perspectives to develop practical, evidence-informed recommendations. The process included defining key clinical questions, reviewing the literature, formulating evidence-based statements, and reaching consensus through structured discussions and formal voting.

RESULTS: A total of 35 authors contributed to the development of these guidelines, with 33 experts participating in the formal consensus process. Altogether, 19 recommendations were generated, with all of them achieving 100% agreement. These recommendations were informed by a comprehensive review of systematic reviews, randomized controlled trials (RCTs), and observational studies encompassing a broad range of regenerative therapies.

Evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to determine certainty levels. Both qualitative and quantitative analyses were applied to synthesize the best available data, resulting in evidence-based recommendations summarized below.
Intradiscal Injections (PRP): 
Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: Moderate
Intradiscal Injections (BMAC): 
Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: Moderate
Epidural Injections (PRP): 
Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: Moderate
Facet Joint Injections (PRP and MSCs): 
Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation: Moderate 
Sacroiliac Joint Injections (PRP): 
Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation:  Low
Functional Spine Unit Injections
Evidence Level: Very Low; Consensus-Based Clinical Recommendation:  Low

LIMITATIONS: The primary limitation of these guidelines is the scarcity of high-quality studies, with much of the available evidence derived from small or heterogeneous trials.

PRECAUTIONS: Regenerative therapies should be considered only after a thorough diagnostic evaluation confirming clinical necessity. Treatment decisions must account for the patient’s medical condition, preferences, and expectations. Patients should be fully informed about the nature, potential benefits, risks, and costs of regenerative treatments, most of which are not covered by commercial insurance.

These therapies may be used alone or in conjunction with other evidence-based modalities, such as structured exercise, physical therapy, behavioral therapy, or conventional medical management. Clinicians must follow all applicable U.S. Food and Drug Administration (FDA) regulations and adhere to safety and ethical standards outlined in these guidelines.

CONCLUSION: Based on current evidence, lumbar intradiscal injections of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are supported by Level III evidence. Lumbar epidural PRP injections are also supported by Level III evidence, while PRP injections for lumbar facet joints and sacroiliac joints are supported by Level IV evidence. Given the emerging status of biologic therapies and the limited quality of existing studies, the panel provides moderate, consensus-based recommendations for the use of all biologics in the lumbar spine.

KEY WORDS: Chronic low back pain, discogenic pain, facet joint pain, sacroiliac joint pain, regenerative medicine, platelet-rich plasma, mesenchymal stem cells, stromal vascular fraction, exosomes, bone marrow concentrate, intradiscal injections, facet joint injections, sacroiliac joint injections, epidural injections, Food and Drug Administration, minimal manipulation

DISCLAIMER: These guidelines do not constitute inflexible treatment recommendations. Clinicians are expected to establish a plan of care on a case-by-case basis, considering an individual patient’s medical condition, personal needs, and preferences, and the physician’s experience. Consequently, these guidelines do not represent a “standard of care.”